United States
   Environmental Protection
    National Institute of
    Environmental Health Sciences
 Pediatric Environmental
  Health Specialty Units
                  Proceedings of the 2007 Children's
                  Environmental Health Workshop:
                  Discover, Treat, Prevent,  Prepare
                  OCTOBER 10-13,2007
                  THE HAMILTON HOTEL
                  14TH AND K STREETS, NW
                  WASHINGTON, DC 20005
   [ National Center for Environmental Research
   I Science To Achieve Results (STAR) Research Program

                                    PSOTECTKG CHILDREN'S HILI
               2007 Children's Environmental Health Workshop:
                         Discover, Treat, Prevent, Prepare

                                   Hamilton Crowne Plaza
                                    1001 14th Street, NW
                                      Washington, DC

                                   October 11-12, 2007

This workshop brings together the expertise and experience of the Pediatric Environmental Health Specialty
Units (PEHSU) of North America and the Children's Environmental Health Centers to explore the latest
research findings and their practical application in community settings. This workshop is sponsored by the
U.S. Environmental Protection Agency (EPA) (Office of Research and Development and Office of Children's
Health Protection and Environmental Education), the Department of Health and Human Services (Agency for
Toxic Substances and Disease Registry of the Centers for Disease Control and Prevention and the National
Institute of Environmental Health Sciences), and the Association of Occupational and Environmental Clinics
in recognition of 10 years of federal effort to protect children's environmental health as called for in Executive
Order 13045, Protection of Children from Environmental Health Risks and Safety Risks.
This anniversary provides the children's environmental health community with an opportunity to reflect on the
progress that has  been made and to formulate our vision for the future of children's environmental health.

8:15-9:00 a.m.
           Thursday, October 11, 2007

Breakfast and Registration

Welcome/Review of Agenda
William H. Sanders III, Dr.P.H.
Director, National Center for Environmental Research, EPA

Dona DeLeon, Acting Director, Office of Children's Health Protection and Environmental
  Education, EPA

Kevin Y. Teichman, Ph.D.
Acting Deputy Assistant Administrator for Science, EPA

Children's Environmental Health:  Looking Backward, Looking Forward
Howard Frumkin, M.D., Dr.P.H., M.P.H.
Director, National Center for Environmental Health, Agency for Toxic Substances and
  Disease Registry, Centers for Disease Control and Prevention
                     Gwen Collman, Ph.D., Chief, Susceptibility and Population Health Branch, Division of
                     Extramural Research and Training, National Institute for Environmental Health Sciences

9:00 - 10:45 a.m.       Session I:  Evolution of Biomarkers for Pesticides:  Examples From the
                      Agricultural Setting
                      Co-Chairs:      Catherine Karr, M.D., Ph.D., Director, Northwest PEHSU
                                     Elaine Faustman, Ph.D., Director, Center for Child Environmental
                                      Health Risks Research

                      In the late 1990s, an epidemic of initially unrecognized organophosphate (OP)
                      poisoning affecting families in eight states helped motivate the development of the
                      PEHSU network to increase the capacity of physicians to identify and prevent
                      adverse effects of environmental toxicants. In recent years, concern has focused on
                      the potential child health implications from chronic, lower level exposure and are a
                      focus of ongoing longitudinal birth cohort studies and exposure pathway studies
                      within the EPA/NIEHS Children's Centers Program. An accumulating evidence base
                      led to recent restrictions in residential use of these products; however,
                      organophosphate insecticides continue to have  extensive use in many agricultural

                      In research  and  clinical settings, biomarkers of organophosphate exposure, toxicity,
                      and susceptibility have contributed to improved  understanding of exposure pathways
                      and adverse health outcomes. The session will discuss: (a) use of pesticide
                      metabolite concentrations to estimate exposure type, extent, and source attribution
                      based on EPA/NIEHS-sponsored studies and CDC population surveillance; (b)
                      strengths and pitfalls regarding the determination of cholinesterase enzyme activity
                      in clinical practice, occupational surveillance, and research as a marker of OP
                      toxicity; and (c) evolving insight into the importance of gene-environment interaction
                      in OP toxicity using recent findings based on paraoxonase 1 studies in the
                      Children's Centers.

                      The key areas for discussion will include the current stage of validation of these OP-
                      related biomarkers and critical missing data/applications to consider in moving the
                      translation of each biomarker forward for clinical and  public health relevance.  The
                      links between research, education, and  risk communication  activities from PEHSU
                      and the Children's Centers will be highlighted.

                                     Elaine Faustman, Ph.D.
                                     Catherine Karr, M.D., Ph.D.
                                     Kim Harley, Ph.D., University of California at Berkeley, Center
                                      for Children's Environmental Health Research
                                     John Furman, Washington State Department of Labor and Industries
                                     Bill Griffith, Ph.D.,  Center for Child Environmental Health Risks Research
                                     Frederica Perera, Dr.PH, Columbia Center for Children's Environmental

10:45-11:00 a.m.     Break

11:00 a.m. - 12:45 p.m. Session II:  Phthalates Exposure in Childhood:  Is There Evidence of Harm?
                      Chair:          Maida P. Galvez, M.D., M.P.H., Mount Sinai PEHSU, and Mount
                                      Sinai Center for Inner City Toxics and Children's Health

                      Phthalates are chemicals added to plastics that impart flexibility and act as a scent
                      stabilizer for a wide range of products—from food packaging and children's toys to
                      personal hygiene products such as shampoos, fragrances, and nail polish.
                      Concerns exist about the potential for phthalates to act as endocrine disrupters,
                      largely based on animal studies and a small but growing body of evidence in human

                      Several countries around the world, beginning with the European Union, have
                      subsequently banned phthalates in children's products. Since then, widespread
                      media reports on the potential harms of toxic toys and other children's products
                      containing phthalates have raised parental anxiety about the impact of
                      environmental exposures on their children.

                      Primary care pediatricians are subsequently faced with clinical questions that are
                      often difficult to answer given the limited medical school training in children's
                      environmental health, particularly in newly emerging exposures of concern such as

                      This session will present clinical scenarios commonly encountered by general
                      pediatricians and PEHSUs regarding questions about phthalates. The goal of this
                      session is to describe:  (a) exposure levels in pregnant women, toddlers, and
                      school-aged children; (b) sources of exposure; and (c) known and potential health
                      outcomes. Data will be shared from three cohorts:  A cohort of pregnant women in
                      New York (Dr. Robin Whyatt, Columbia University Center for Children's
                      Environmental Health); a cohort of 6 to 24-month-old infants from California,
                      Minnesota, and Missouri (Dr. Sheela Sathyanarayana, University of Washington,
                      Seattle, Northwest PEHSU); and a cohort of 6 to 8-year-old New York City
                      children (Drs. Mary Wolff and Maida Galvez, Mount Sinai Center for Children's
                      Environmental Health and Mount Sinai PEHSU).

                      Key areas for discussion will include:  (1) What is the current evidence for adverse
                      health outcomes? (2) What are the research gaps? (3) What health messages on
                      phthalates can we share with families now? (4) What policy issues remain

                      Presenters:    Maida P. Galvez,  M.D., M.P.H., Mount Sinai PEHSU, and Mount
                                      Sinai Center for Inner City Toxics and Children's  Health
                                    Robin Whyatt, Dr.P.H., Deputy Director, Columbia Center for
                                      Children's Environmental Health
                                    Sheela Sathyanarayana, M.D., Northwest PEHSU
                                    Mary Wolff, Ph.D., Director, Mount Sinai Center for Inner City Toxics
                                      and Children's Health

12:45-2:00 p.m.       Lunch (on your own)

2:00 - 3:15 p.m.        Session III: The Evolving Science and Practice of Environmental Management
                      for Asthma Prevention and Care
                      Co-Chairs:    Kimberly Gray, Ph.D., National Institute of Environmental Health
                                    Ley/a E. McCurdy, National Environmental Education Foundation

                      Asthma is a chronic respiratory disease characterized by episodes of inflammation
                      and narrowing of small airways. Childhood asthma, in particular, continues to be a
                      major, vexing public health problem in the United States. Low-income populations,
                      minorities, and children living in inner cities still experience disproportionately higher
                      morbidity and mortality due to asthma. Asthma's effects on children and
                      adolescents account for millions of lost days of school missed annually and cost
                      more than $3 billion per year to treat.  According to the Centers for Disease Control
                      and Prevention in 2005, prevalence rates for childhood asthma peaked at 8.9
                      percent;  more than 6 million of the nation's children. Even so, there have been
                      important gains recently, including a reduction in childhood deaths from asthma
                      attacks, a leveling of hospitalizations, improved patient education, and evidence of
                      earlier clinical recognition and treatment.

                      Currently, there are neither known preventions nor cures for asthma.  However,
                      avoiding environmental agents  that promote or exacerbate asthma attacks is one of

                      the primary goals of good asthma management. Considerable research within the
                      EPA/NIEHS Children's Centers has primarily focused on four areas: (1) household
                      interventions and avoidance of environmental triggers, (2) exposure and effects of
                      air pollution, (3) gene-environment interactions, and (4) mechanisms of early
                      immune deregulation and subsequent asthma risk.
                      This session will: (1) review potential mechanisms (immune, epigenetic) for the
                      effects of prenatal and early postnatal exposure on asthma outcomes, and the
                      ongoing mechanistic work being performed by the Children's Centers; and (2)
                      highlight currently recommended household environmental management strategies
                      most useful for clinical settings based on the 3rd Expert Panel Report of Guidelines
                      on Asthma issued August 2007.

                      The discussion will broaden to include recent research findings of Children's
                      Centers, including the impact of chronic exposure to air pollution and the
                      contribution of genetic vulnerabilities in an open-session format.

                       Presenters:    David Rowson, Office of Air and Radiation,  EPA
                                     Rachel Miller, M.D., FAAAAI, Columbia Center for Children's
                                      Environmental Health

                      Discussant:     Elizabeth Matsui, M.D., M.H.S., Center for Childhood Asthma in
                                      the Urban Environment
                                     James M. Seltzer, M.D., University of California, PEHSU

3:15-3:30 p.m.        Break

3:30 - 5:15 p.m.        Session IV: Early Life Exposures to Metals and Neurotoxic Outcomes
                      Co-Chairs:      Isaac Pessah, Ph.D., Director, University of California at  Davis,
                                      Center for Children's Environmental Health
                                     Nigel A. Fields, M.S.P.M., National Center for Environmental
                                      Research, EPA

                      There has been significant public health progress in reducing chronic high level
                      exposures to metals, such as lead  and mercury, which can cause neurological
                      damage at any age. For instance,  today most children in the United States maintain
                      average blood lead levels well below the action level of 10 ug/dL. This has been
                      accomplished largely through state and local education and advisories,  multimedia
                      public health campaigns, and federal regulation. However, there is increasing
                      evidence that early life exposures to toxic metals, particularly during fetal
                      development, may contribute to behavioral effects and adversely affect cognitive
                      functioning well into adult life.  There also is growing concern regarding  the social
                      context of exposure, or non-chemical stressors, which may modify the uptake and
                      neurotoxic effect of metals such as lead, mercury, and manganese, both pre- and
                      post-natally. Yet, currently there is limited ability to identify and translate clinically
                      significant prenatal biomarkers of exposure, susceptibility, and effect that could
                      better elucidate risks of metal exposures during pregnancy.

                      The purpose of this session is to: highlight recent findings of the long-term effects of
                      metals and  metal mixtures; discuss the utility of perinatal biomarkers of lead and
                      mercury; and consider modifying factors that might offer additional protection or
                      confer additional risk to children. Based on three longitudinal cohorts and one case-
                      control study, this session will  explore:  (1) the plausible interactive  effects of metals
                      and psychosocial stresses on  neurodevelopment; (2) the use of new mercury
                      exposure biomarkers and epidemiological approaches in autism etiology research;
                      (3) the long-term behavioral consequences of fetal and childhood exposures to lead,
                      resulting in criminality and increased societal risks; (4) the impact of early  exposure
                      to lead on adult cerebral cortical  anatomy and function as revealed  by advanced
                      neuro-imaging techniques; and (5) the interactive effects of exposure to multiple
                      metals on neurodevelopment.

                      Panel and Audience Discussion Questions:  What are the key window periods of
                      concern for fetal exposure to metals? What factors confer added protection or
                      increased risk from early life exposures to metals? How should  the long-term effects
                      of metal exposures inform public health actions during early childhood
                      Presenters:    Irva Hertz Piciotto, Ph.D., Deputy Director,  University of California
                                      at Davis, Center for Children's Environmental Health
                                    Robert Wright, M.D., New England PEHSU and Harvard Center for Metal
                                      Mixtures and Children's Health
                                    Kim Dietrich, Ph.D., Cincinnati Children's Environmental Health

5:30 p.m.              Reception and 3rd Annual EPA Children's Environmental Health Excellence
                      Award  Ceremony (Open Invitation)

                      Dr. William H. Sanders III, Presiding

                      The Children's Environmental Health Excellence
                      Awards recognize ongoing and sustainable
                      dedication to, and notable leadership in,
                      protecting children from environmental health
                      risks at the local, regional, national, and
                      international level.  Excellence Awards are
                      presented to groups or individuals that exemplify
                      invaluable leadership in the protection of children
                      from environmental health risks. There are 10
                      winners in 2007, 7 in the health care provider
                      category, 1 for schools, 1  for corporate
                      leadership, and 1 for research.

                      The Children's Environmental Health Champion is an  honorary award presented to
                      individuals to recognize their outstanding efforts and commitment to advancing
                      environmental health issues. The 2006 Children's Environmental Health Champion
                      award was presented to Philip J. Landrigan,  M.D., M.Sc., and in 2005 our Champion
                      Award winner was Ramona Trovato.

                      Who will it be for 2007? Join us and find out!

                                   Friday, October 12, 2007

7:30 a.m.              Breakfast

8:30 - 9:30 a.m.        Session V: Transportation, the Built Environment, and Children's Health

                      Moderator:     Joanne Rodman, Acting Director, Child and Aging Health
                                    Protection Division, OCHPEE

                      This session will explore trends in population demographics,  how and where
                      development occurs, the explosive growth in international trade, and the anticipated
                      impacts on public health, the environment, transportation, and infrastructure
                      planning.  There will be a  more detailed look at trends in school  siting with
                      relationship to roadways and other factors and discussion of the implications of
                      those trends on efforts to  develop healthy communities.  The session will examine
                      how a school's site and its context within a community can affect children's health,
                      as well  as the environment, economic development, land use, and transportation.
                      Recent studies on proximity to traffic and adverse health effects will be discussed,
                      as well the health and community impacts of port and  "goods movement" (freight
                      transportation) expansion in many U.S. cities. Possible points of intervention for the
                      public health community on this issue also will be discussed.

                      Tim Torma, EPA, Office of Policy, Economics and Innovation
                      Andrea M. Hricko, M.P.H., University of Southern California, Center for
                        Children's Environmental Health

9:30 - 10:00 a.m.       The National Children's Study: Opportunities for Adjunct Studies
                      Marion Balsam, M.D., Research Partnerships Program Director, National Children's

                      As the National Children's Study proceeds, scientific knowledge will evolve and the
                      Study will serve  as an appropriate platform on which to build additional scientific
                      studies. Investigators from various sectors will propose adjunct studies. Such
                      studies will enhance the breadth, depth, and value of the Study and will assure
                      continued interest of a diverse group of investigators, which is critical to the overall
                      success of the Study.

                      An adjunct study involves a portion of the National Children's Study cohort, utilizing
                      individually or in combination, any of the following: The Study participants, their bio-
                      specimens, or their environmental samples. Adjunct studies can take place at one
                      or more Study Centers, on all or a portion of their Center participants. Adjunct
                      studies generally will be initiated and planned outside of the Study protocol planning
                      process and funded with non-Study funding; that is,  by such mechanisms as
                      government grants (for example, R01) applied for by the initiator, by intramural
                      federal resources, through public private partnerships,  or from other sources. To
                      preserve the quality and integrity of the National Children's Study, all proposals for
                      adjunct studies will receive rigorous review. This presentation will include a brief
                      overview of adjunct studies and of the review and approval process.

10:00-10:15 a.m.     Break

10:15-11:15 a.m.     Session VI:  Children's Protection in the Aftermath of a Natural Disaster:
                      Tools for Recovery and Communicating Risks
                      Chair:          Debra Cherry,  M.D., M.S., University of Texas Health Center at
                                        Tyler, Southwest PEHSU

                      Hurricane Katrina, which struck the Gulf Coast on August 29, 2005, has been called
                      the most devastating natural environmental calamity in U.S. history.  More than
                      354,000 homes  along the Gulf Coast were destroyed or damaged beyond repair.
                      Katrina damaged more than 200 sewage treatment plants and 140 oil and gas
                      platforms and leached hazardous chemicals and fuels from hundreds of small
                      businesses as the floodwaters passed over them. Rampant mold growth, mountains
                      of debris, and widespread cleanup, demolition, and construction projects followed.
                      Some residents  were housed "temporarily" in FEMA trailers with hastily assembled
                      indoor materials that off gassed high levels of formaldehyde.  Many New Orleans
                      residents left the area permanently.

                      This session will describe some of the efforts of a Gulf Coast pediatrician, NIEHS
                      scientists, and PEHSU clinicians to respond to this calamity.  Dr. Scott Needle
                      (pediatrician, relocated from Bay St. Louis, Mississippi to Florida) will describe via
                      Web conference his experience on  the front lines of the disaster, the disaster
                      preparedness document he prepared on behalf of AAP, and his federal testimony on
                      the health effects of formaldehyde in FEMA trailers.  Dr. Marie Lynn Miranda
                      (scientist and CIS expert, Duke  University) will describe the NIEHS Hurricane
                      Response Portal, a research and planning tool for the Gulf Coast, which overlays
                      multiple geographic and demographic features, such as location of hazardous waste
                      sites, racial composition, and  extent of flooding. Dr. Debra Cherry (occupational
                      medicine physician from the Southwest PEHSU) will briefly present fact sheets on
                      sludge, formaldehyde, and mold, as well as the PEHSU/AAP guidelines for returning
                      children to previously flooded areas.

                      Key areas for discussion will include: (1) How should federal agencies communicate
                      with local clinicians in the aftermath of a natural disaster? (2) What types of tools
                      are most useful?  (3) What environmental health risks were overblown, and which
                      were understated in the aftermath of Hurricanes Katrina and Rita?

                      Presenters:    Debra Cherry, M.D., M.S., University of Texas Health Center at
                                      Tyler, Southwest PEHSU
                                    Marie Lynn Miranda, Ph.D., Director, Duke University Southern
                                      Center for Environmentally-Driven Disparities in Birth Outcomes
                                    Scott Needle, M.D., Pediatrician, formally of Bay St. Louis, MS

11:15 a.m. - 12:15 p.m. The National Forum on Children and  Nature

                      Key Note Address:  Lawrence A. Selzer, President and Chief Executive Officer,
                                           Conservation Fund
                      Introduction and Discussant:  HowardFrumkin, M.D., Dr.P.H., M.P.H.

                      Launched in June 2007, the National Forum on Children and  Nature will involve
                      governors, mayors,  corporate CEOs, heads of environmental organizations, and
                      leaders from health  and education institutions, and will invest several million dollars in
                      projects with on-the-ground tangible results that address the issue of children's
                      isolation from nature. The  Forum will identify 20 nationally significant demonstration
                      projects in four key areas of health, education, the built environment, and
                      media/culture that, individually and collectively, will provide substantial steps toward
                      improved children's  health  and environmental stewardship.

12:15 - 12:30 p.m.     Closing Remarks:  Dr. William H. Sanders III, EPA

Many thanks to the honorary workshop co-chairs: William Sanders and Howard Frumkin

Also special thanks to the workshop planning committee: Nora Conlon, Elaine Faustman, Maida Galvez,
Kimberly Gray, Michael Hatcher, Catherine Karr, Leyla McCurdy, Ketna Mistry, Jerome Paulson, Isaac Pessah, and
Maryann Suero

And thanks to the Washington, DC, coordinating team: Martha Berger, Richard Callan, Cerena Cantrell, Tina
Conley, Paula Davis, Nigel Fields, Bettina Fletcher, Carolyn Hubbard, and Susie Warner

           2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare

                2007 Children's Environmental Health Workshop:
                          Discover, Treat, Prevent, Prepare

                                  Hamilton Crowne Plaza
                                    1001 14th Street, NW
                                     Washington, DC

                                    October 11-12, 2007

                                  MEETING SUMMARY

OCTOBER 11,2007


The U.S. Environmental Protection Agency (EPA) 2007 Children's Environmental Health Workshop:
Discover, Treat, Prevent, Prepare was held on October 11-12, 2007, in Washington, DC. The workshop
brought together a diverse group of clinicians, researchers,  and health advocates from academic, gov-
ernment, and nonprofit organizations. Participants discussed issues in clinical practice, ongoing research
in children's environmental health,  and opportunities for translating scientific findings. The workshop
also  served as  a  stimulus for increased collaborations among the Pediatric Environmental Health
Specialty Units (PEHSUs) and the Centers for Children's Environmental Health and Disease Prevention
Research. Approximately 133 individuals attended.

Welcome and Review of the Agenda
Nigel Fields, William H. Sanders, III, Dona DeLeon, and Kevin Y. Teichman, U.S. EPA; Paula
Davis, Association of Occupational and Environmental Clinics (AOEC)

Mr. Fields thanked attendees for their participation. He noted that the  10th anniversary  of Executive
Order  13045, Protection of Children  from  Environmental  Health  Risks  and Safety  Risks, was  an
opportune time  to celebrate the progress made in  children's environmental health (CEH) and to align
perspectives for the  future of this field. He invited participants to  engage  workshop speakers in their
discussions about how to further CEH protection.

Ms. Davis,  Coordinator of the Pediatric Environmental Health Specialty  Units Program (PEHSU) wel-
comed  presenters and workshop participants. She  expressed her interest  in collaborating  with PEHSU
colleagues and other scientists involved in CEH to help bridge the gap between research and practice.

Before  his recent appointment as Director of the National Center for Environmental Research (NCER),
Dr. Sanders previously  worked directly with the PEHSUs and indirectly with the Children's Environ-
mental  Health Centers  (CEHC) in his role as Acting Director of  the Office  of Children's Health
Protection and Environmental Education. He noted the variety of constituents in attendance and remarked
that it is a  great opportunity for bringing together representatives from  the PEHSUs with the CEHC
Directors in a central venue. He presented an overview of the workshop agenda, explaining the nature of
each session.  Dr.  Sanders  also invited participants to attend the  Third Annual Excellence Awards
Ceremony at end of the first day.

Ms. DeLeon explained that she is new to the Office of Children's Health Protection and Environmental
Education but has spent many years at EPA, including working with and examining the delivery system at

        The Office of Research and Development's National Center for Environmental Research

            2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
the state and local levels. Implementation of environmental policy is taking place at the local level; how
regulation implementation is translated at the local level and communicated to the public is critical to
keep environmental progress moving forward. This audience plays an important role in communicating
health risks and promoting the science that underlies decision-making to the public working with families
and children. She congratulated attendees for the progress that has been made and thanked them for their
continuation of these efforts. She  welcomed  the  international  visitors and commented that she  looks
forward to learning more about  children's  environmental health  issues and how  EPA  can  assist
researchers in advancing these issues.

Dr. Teichman welcomed participants and remarked that the CEH protection community experienced
another tremendous year of growth; he noted that  it was appropriate that the workshop was held during
Children's Health Month. He  also welcomed Dr. William Sanders to EPA's Office of Research and
Development (ORD) and expressed his gratitude to the Center for Children's Environmental  Health and
Disease Prevention  Research;  the National  Institute  of Environmental Health  Sciences (NIEHS);
PEHSUs; the Agency for Toxic Substances  and Disease Registry (ATSDR); AOEC; and the  new health
care provider capacity-building grantees and Children's Environmental Health Champion Award winners.

The mission of EPA is to protect human health and the  environment. In attempting to achieve this goal,
the Agency is examining one of the  most vulnerable populations with increased specificity. There is a
wide range of genetic susceptibility among newborns and young children to exposure from household or
agricultural pesticides. Where a child lives within  the urban environment may significantly influence or
impact his or her exposures and health outcomes. With the passing of several federal mandates, EPA has
emphasized the identification of child-specific exposures, health risks, and protective actions for more
than a decade. Within ORD, these mandates have stimulated a wide array of research activities, with  the
purposes of studying how chemical exposures change across life stages; gaining a greater understanding
about the genetic factors that contribute to children's vulnerability to air pollution, pesticide exposures,
and heavy metals; validating novel methods for both aggregate and cumulative exposures to single and
multiple  chemical,  biological,  and  radiological agents; discovering,  translating,  and  employing
biomarkers of exposure effect and susceptibility; and promoting cost-effective sustainable household- and
community-level interventions.

EPA scientists and their academic partners have applied their expertise to these efforts because children
may be at increased risk from environmental influences as a result of their vulnerable developing systems
and enhanced exposures to  many  agents. These  environmental influences include the quality of air,
ingested lead,  and exposures to chemicals and mold; all of these factors are within society's power to
control. ORD  researchers  have contributed to improving CEH  in many ways. The Stochastic  Human
Exposure and Dose  Simulation Multiscale Model is now used as a primary tool for simulating exposures
to a variety of chemicals that  enter the body to determine how best to advise the public on reducing
children's exposures to toxic compounds. During the past 10 years,  EPA has improved the ability to
monitor chemical exposures and assess the effects  based  on the  development, validation,  and imple-
mentation of biological markers. EPA scientists and those supported by the Agency  are leading efforts to
validate noninvasive biomarkers and to apply them in epidemiologic studies and clinical  settings.  ORD
also is contributing to the Agency's next Report on the Environment by developing the scientific basis for
the use of health outcomes to measure and evaluate environmental policy decisions.

ORD is only one contributor to improving the understanding of CEH; community partners play a critical
role in informing,  implementing,  and translating research findings.  Workshop participants have  the
opportunity to discuss  findings and clinical experiences and translate those experiences  for advancing
more protective medical guidance in environmental policy into the future. Today's sessions, which focus
on the translation of research and clinical insights regarding organophosphates (OPs), phthalates, asthma,
and exposures to metals,  will  specifically concentrate on prenatal and  early life exposures  and  the
        The Office of Research and Development's National Center for Environmental Research

            2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
subsequent health effects associated with these exposures. The next day's sessions will examine what lies
ahead for researchers, clinicians, and health advocates as increasingly complex public health challenges
that also will impact children's health emerge. These challenges include persistently high rates of low
birth weight and preterm births; increasing rates of neurobehavioral disorders in young children, such as
autism and attention  deficit hyperactivity disorder (ADHD);  increasing body burdens of potentially
endocrine-disrupting compounds; escalating prevalence rates for obesity and type II diabetes; growing
disparities between low-income and minority groups to chemical exposures; the risks of climate change;
the emergence and application of nanotechnology; and complex trends in urbanization. EPA will need
partners in determining the environmental factors and related health outcomes of these issues.

ORD will continue to work closely with the Centers for Disease Control and Prevention (CDC), National
Institutes of Health (NIH), and international collaborators such as the World Health Organization (WHO)
to systematically discover ways to protect children in a rapidly  evolving world. The National Children's
Study (NCS) holds much promise for gaining a deeper understanding of these complex issues and to
make better, more targeted decisions for promoting healthier environments. The NCS  represents a truly
unprecedented collaboration among government agencies, private industry and foundations, community
leaders, and university-based  scientists around the nation devoted to improving children's health. EPA
conducted  and supported much  of the  science  that  laid the foundation for this  ambitious  study.
Researchers from the CEHCs participated in workgroups that developed the core hypotheses for the
studies, and the Centers also  collectively published "Lessons Learned" papers to offer guidance to the
NCS for practical approaches to sustaining long-term studies and interpreting complex data.

Last week,  EPA joined the National Institute of Child Health and Development (NICHD) in announcing
the 22 Health Study Center awards, which joined the previously awarded Vanguard  Centers in officially
launching the study next year. As the research community moves forward to build on the past decade of
success, it is clear that meeting these challenges will require strong, committed partnerships that better
link research questions, health care practice, and environmental health.

Children's  Environmental Health: Looking Backward, Looking Forward
Howard Frumkin, CDC, and Gwen Collman, NIEHS

In 1993, the National Academy of Sciences published Pesticides in the Diets of Infants and Children.
This report helped establish the scientific basis for the CEH  movement. Executive Order  13045 is a
milestone in the movement, but since its enactment, the world has changed in many ways. For instance,
10 years ago, people did not routinely discuss the enhanced vulnerability of children, and preparedness
was not a commonly used term in the public health world. Much work has been accomplished in the CEH
field during the past 10 years in the areas of research, education, and service. Disease-specific research,
community-based participatory research, research on the combination  of  genetic and environmental
factors, and studies on vulnerable populations have expanded.  Education has been  extended to include
fellowship training, and the field has seen an increase in the publication of books,  papers, and Web sites
related to CEH. The development of community networks, PEHSUs, and technical  tools have added to
the list of services that the scientific community provides to the public, but it is time to evaluate these
accomplishments  by asking what  they  have achieved in terms of improving children's health. Are
children healthier now? Do health care providers and parents know how to provide  children with safe and
wholesome environments more effectively than they did 10 years ago? Has there been a continuing record
of policy-making reflecting the importance of CEH?

This month, October 2007, marks the 10th anniversary of the Executive Order, and the CEH community
is entering  a new  decade with the chance to reinvent, reinvigorate, and  re-expand efforts and move from
an individual clinical approach to a more encompassing legacy approach of caring for future generations.
Biomonitoring is a well-established tool for determining known toxicants in the bodies of children.  This

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tool will be instrumental in focusing future research trends by measuring decreases in current chemicals
of concern and identifying  possible emerging toxicants.  Genetic science  will transform the field as
research continues and scientists  deepen their understanding  of gene-environment  interactions. In
addition, there appears to be a change in the political climate that is more sympathetic to CEH.  The child
health  community must take advantage of these advances to confront current and future challenges.
Challenges during the next 10 years include poverty, changing chemical toxicity, dealing with the built
environment, climate change, mental health burdens, and communication.

Poverty and lack of insurance are two of the most important threats to children's health, as underscored
by the American Cancer  Society's 2007  public relations theme,  "Access  to Health Care."  The built
environment has impacted children's health  by engineering physical  activity out of neighborhoods and
communities.  Children  and adults now must drive  to  most  destinations, including  grocery stores,
pharmacies, shopping malls, and schools. Low physical activity has been linked to childhood obesity and
an increase in diabetes, and the increase in vehicle traffic is adding to environmental  pollution. The built
environment  also discourages  childrens from  spending time outside. The author of Last Child in the
Woods advocates "saving  our kids from nature-deficit disorder" and maintains that spending time in
natural settings is an  important part of a healthy childhood. One  of the mechanisms of the benefits of
nature contact seems to be through attention-restoration theory, which states that attention is focused and
distractions are minimized when children have the chance to be outside. This book has given rise to some
very interesting efforts. The  Children and Nature Network links people working to promote initiatives at
the state level, including the "Leave No Child Inside" initiative. A number of federal agencies, such as the
U.S. Fish  and Wildlife  Service, have developed programs  about  reconnecting children and nature. An
initiative called "The National  Forum on Children and Nature" seeks to support 20 nationally significant
demonstration projects across the country that will restore kids into  national settings, with a focus on
underserved and minority children. Research on the health evidence of these initiatives should be part of
the CEH portfolio.

Climate change is an important  and growing  environmental  health concern. In  addition to potential
physical effects, children now face potential psychological  effects, including some  effects that may stem
from the fear associated with global warming. Other psychological effects already have been seen in the
aftermath  of recent hurricanes, which are  predicted to become more  severe with global warming. This
kind of message in the media is becoming more common now, with rather apocalyptic  narratives about
climate change. Journalistic  accounts of schools have  described evidence of terror in children  about the
world and what it has in store for them.  This must be considered because climate change is an issue that is
going to remain for a long time. The manner in which it is discussed either will  scare  and immobilize
people, or it will spur them to constructive action; the  right message must be promoted. The reactions of
adults influence children's reactions. Aftereffects of climate-related events must be  considered as well;
the biggest health burden of Hurricane Katrina,  in retrospect, is the mental health burden.  The anticipation
of bad things happening, the aftermath, and the post-traumatic phase are serious mental health concerns
that threaten children, and this needs to be part of CEH thinking.

"The Death of Environmentalism," an essay by  Ted Nordhaus and Michael Shellenberger, was considered
a "big picture" piece on environmentalism. It challenged some of the basic assumptions of contemporary
environmentalism. The book-length expansion of that essay, Breakthrough,  is provocative reading, and
some of its points are very relevant to children's environmental health.  Many CEH messages are negative:
stopping the bad rather than creating the good. The authors recommend articulating a positive, compelling
image of a healthy, wholesome world,  rather than focusing so much on the  negative. Positive  messages
are compelling and motivating to the public. Additionally, the challenge of climate  change is so massive,
global, and complex that it can only be overcome if the issue categories of the past are discarded and an
aspirational vision of the future is embraced. According to the authors, environmentalists should think
about job  creation, economic  development,  law enforcement, and other important  issues traditionally
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outside the environmental arena. A similar approach may well be advisable for CEH. In communities
where toxic exposures for children are a concern, poor education, joblessness, or squalor in the physical
environment often are more important problems than the toxic exposures. The more globally children's
problems can  be addressed, the better they will be managed;  broad thinking and getting outside of
traditional categories can be beneficial. Climate change calls for expanded thinking.

One method by which CEH research portfolios can be expanded is to leverage opportunities with other
partners, such  as the U.S. Fish and Wildlife Service, which is actively involved in getting children back
into the outdoors; the U.S. Department of Housing and Urban Development (HUD), which attempts to
improve the quality of housing; and the U.S. Department of Education, which is concerned with healthy
schools. Leveraging of opportunities and development of new partnerships must be creative, as concerns
increase without increasing resources.

Dr. Collman explained that NIEHS has a strong portfolio in research areas that are now classically part of
the rubric of CEH, such as basic mechanisms of toxicity during development, early life, and  in organ
systems related  to  diseases. The executive orders, reports,  and regulations provided an impetus for
moving the science forward  and  moving  individual scientific  inquiries in individual laboratories to
partners across a spectrum of science. These efforts were furthered by the creation of the CEHCs, which
bring together scientists of different disciplines  to  work with local health advocates  and community
partners. Through  multidisciplinary research and  outreach  projects, the Centers are  investigating
environmental health  challenges facing children  and families in  their  community  settings. These
partnerships would not be complete without the health care community. Today, this collective network of
research, community, and clinical partners can be proud of the training and development programs that
are preparing future scientists and health care professionals, including  residents,  fellows, and academic
physicians in becoming tomorrow's experts and leaders in CEH.
Co-Chairs: Catherine Karr and Elaine Faustman, University of Washington

Dr. Karr stated that it was a pleasure to open the first workshop session. The topic of the session is the
evolution of biomarkers for pesticides with examples from agricultural settings. The session speakers are
accomplished leaders from the public health, research, and clinical sectors who will discuss their experi-
ences with biomarkers with the focus on a specific group of pesticides, the OP insecticides. Despite recent
decreases in home and garden use, these insecticides continue to be used heavily in agriculture and are of
great interest in the Pacific Northwest because  of orchard crop production that relies intensively on OP
use. OPs also are of interest because of their legacy of acute toxicity in humans; they are the pesticides
most often  implicated  in  symptomatic  illness. Another  reason  to  consider OP  exposures is the
accumulating evidence of neurodevelopmental toxicity related to relatively  low chronic exposures in
children. This provides a framework for considering the application and use of biomarkers. Biomarkers
provide a context for understanding the  pathway  from release of an organopesticide  in  a child's
environment to the potential for development of clinically significant disease  or prognosis. This session
will explore biomarkers of exposure in  terms  of internal dose measures  using urinary metabolite
monitoring,  biomarkers of biologically  effective dose or early biological effect, and biomarkers of
susceptibility based on genetic polymorphisms in the population.

PEHSUs receive a number of questions from parents, pediatricians, public health officers, federal agency
leaders, and policy-makers  from "Should I have my  child tested?"  to "Should we  have  a national
monitoring program for agricultural workers?"  Today  researchers  are  at the  stage  of validating
biomarkers and must concentrate their efforts on finding ways for various  sectors to utilize these data.

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Efforts to use biomarkers in population-based monitoring in the States of Washington and California for
occupational surveillance  may inform the following questions: Should we  have a national  medical
monitoring program for agriculturally exposed workers? What would such a program constitute? Lastly,
from a risk assessment perspective, policy-makers may ask researchers:  Can we use biomonitoring to
evaluate  whether  regulation  of diazanon  and chlorpyrifos  (CPF) has reduced exposure  in at-risk
populations such as children?  Policy-makers  may follow the  unfolding story  of the paraoxonase gene
(PON1) as an effect modifier  and  ask:  Should regulatory decision-making incorporate evaluation and
protection of the most genetically vulnerable  subset of the population?  These  are  questions to consider
during the  presentations.  The presenters  will  provide  insight  into  progress  toward validation  of
biomarkers and their utility as well as various limitations and knowledge gaps that need to be overcome,
so that researchers can move forward to increase the clinical public health and  risk assessment relevancy
of biomarkers.

Biomarkers of Pesticide Exposure: Lessons for Children in Agricultural Communities
Elaine Faustman, University of Washington

Dr. Faustman stated that her presentation would focus on some of the biomarkers of pesticide exposure
and some of the lessons for children in agricultural communities, including exposure to internal dose,
biologically effective does, early biological effect, altered structure and function, clinical disease, and the
relationship with biomarkers of exposure and biomarkers of effect. In Washington State, OPs are used on
apple and potato crops. OPs have various structures that differ by ethyl and methyl moieties,  and up to 40
different OPs are in common use. The differences in patterns of the methyl and ethyl group metabolites
can allow for the tracking of sources and attributable uses of these pesticides. Linking this information
within the exposure response biomarker paradigm is important. Agricultural pesticides and contributions
of occupational factors to home, adult, and child contamination will be discussed.

The  complex  series  of metabolites that are  formed following OP exposure presents a challenge to
examining  and interpreting what a biomarker of exposure might mean from the environment versus an
internal dose of biomarker (e.g., urinary metabolites). Genetic polymorphism in the enzymes involved in
the metabolism of these compounds present significant challenges, but modeling approaches that measure
specific and nonspecific metabolites from OPs allow researchers to compare exposure markers. National
Health and Nutrition Examination Survey (NFIANES) data show U.S. population averages and show that
children's exposures are higher than average adult exposures, and this becomes important if the exposures
remain elevated over multiple  years. In terms of assessing children's exposure based on the take-home
pathway, this is the hypothesis that was put forth:  Adult workplace exposure increases pesticides in dust
in vehicles  and  homes and, therefore, to children through  direct physical contact with the adults and
indirectly through contaminated homes and cars.  For example, a study  of homes  and vehicles  of
farmworkers in the Pacific Northwest found that the workers had higher levels of pesticides in the dust of
their vehicles and  homes and  OP markers one to two orders of magnitude higher than U.S. averages.
Their children's levels also were skewed to higher values compared with NHANES data. Modeling across
specific metabolites allows researchers to detect high-risk exposure subgroups. Another study examined
various crops and the distributions of specific metabolites in nonfarmworkers and farmworkers adults and
children. Results showed a higher association of OP metabolites among those  working with pome fruit,
and this was  identified as a  potential place for intervention.  All  of the  correlations were positive,
illustrating a strong workplace  take-home pathway. Using these models, sources of where the metabolite
was attributable to child exposure were identified. These data have informed decisions about intervention
procedures  and  allows targeting  of populations that have been neglected in terms of public health

Two  longitudinal  studies measuring OP  metabolites  revealed another  issue involved in biomarker
analyses:  variability. The variability was less between children than the variability within an individual

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child;  metabolites will vary  considerably following  repeated  sampling of children.  Within-person
distributions are wider than distributions among a whole population. This has important ramifications in
understanding the potential environmental effects of certain agents. Because there are a variety of factors
(e.g., half-life, dynamics of exposure, and continued exposure), sampling approaches must be considered
that increase understanding of how individuals versus populations are being exposed.

Biomarkers of exposure cannot be used for all  types of studies, but they are very useful for understanding
the patterns of exposures and source attribution.  Other studies may be necessary to identify highly
exposed groups and plan interventions. EPA studies will allow researchers to link multiple sampling of
exposure and internal dose with potential early markers of response, such as enzyme changes and gene
expression markers.  Physiologically based  toxicokinetic  models  are  being  built  for  OPs, with
polymorphic information being added at multiple stages for the myriad of enzymes  that are involved in
OP metabolism. This is important so that genotypes  can be used to help identify at-risk populations and to
determine what these differences may mean  for exposure and responses. Once these  tools are further
developed, they can be used for research and  clinical applications. Dr. Faustman's group will be testing
the hypotheses  of how  much knowledge  about the  genotype-phenotype  makes  a difference  in
understanding differences in between-person variability and how much knowledge about gene expression
contributes to  understanding  responses  within the same person over  time.  Future work includes
identifying the  genotype and phenotype for key genes that metabolize  OPs to improve prediction of
exposure  response  and  at-risk  individuals in  agricultural  communities.  Learning  more  about
polymorphisms of oxidant responsive pathways will allow researchers to better evaluate the potential for
genomic biomarkers of early  response to be linked with OP metabolites  of exposure, better predict
relationship of biomarkers of  effect (e.g., acetylcholine) to respond in a dose-response  manner to  OP
exposures in adults and children, and better predict  whether "omic" biomarkers of disease are correlated
with OP exposure.


A participant requested clarification on the comment regarding how exposure measurement techniques
may need to be modified for assessment of chemicals with short chemical half-lives. Dr. Faustman replied
that the NCS holds a lot of promise  to look at longitudinal exposures, but there are unique questions for
some  agents, for  which the exposure  and  compounds are dynamic enough that additional assessments
could be used in the NCS to answer some of these more specific questions. Her presentation illustrated
the kind of information that can be gained from longitudinal studies versus specific studies and how this
information can be integrated to build a cohesive picture.

A participant asked if the study examined children under age 6. Dr. Faustman  replied that the  study
included younger  children but did not examine crawling behavior.

A participant asked Dr. Faustman to discuss intervention and evaluation studies regarding the take-home
pathway conducted at the University of Washington Center. Dr. Faustman indicated that a paired study
was conducted where interventions were performed at the community- and household-level. The data are
being analyzed, but early results show positive associations with intervention actions taken in the homes.
OP Pesticide Exposures and Neurodevelopment in Children From Farmworker Families
Kim Harley, University of California at Berkeley

The  Center  for the Health  Assessment of Mothers and Children of Salinas (CHAMACOS) study is a
longitudinal birth cohort study of Mexican farmworker children and their mothers in the agricultural
Salinas Valley region of California. The goals of this study were to:  (1) estimate source and pathways of

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OP pesticide exposure and levels  of in utero and postnatal pesticide exposures in children  living in
agricultural communities; and (2) determine the relationship of this exposure with neurodevelopment,
growth, and  respiratory  disease. The  Berkeley  team measured biomarkers  of OP exposure  using
dialkylphosphate (DAP) metabolites measured in maternal and child urine. Increasing age, proximity to
agricultural fields, and increased consumption of fresh fruits and vegetables were associated with higher
DAP levels in young children in this cohort.  Prenatal and child DAP levels were compared with early
childhood neurodevelopmental and neurobehavioral outcomes using the Brazelton Neonatal Behavioral
Assessment Scale, Bayley Scales of Infant Development,  the Wechsler Preschool and Primary Scale of
Intelligence (WPPSI-III), and the Child Behavior Checklist (CBCL). Reflexes in neonates  were more
likely to be abnormal in association with high maternal DAPs, but no associations were  established
between prenatal DAPs and six of the other seven Brazelton clusters. In addition, as the mothers' prenatal
levels increased, Bayley Mental Development Index scores decreased in children at 24 months of age.
Higher  prenatal DAPs were also  associated with increased likelihood  of Pervasive  Developmental
Disorder, as assessed by the CBCL at 24 and 42 months of age. Findings were driven primarily by the
dimethylphosphate,  as opposed to diethylphosphate  metabolites. These  results  were  compared with
similar studies at Mt.  Sinai Hospital and Columbia University in New York City (NYC). Although these
studies looked at different populations, the results mirrored results found in California. The NYC cohorts
were made up of Mexican,  Puerto  Rican, and Dominican  Hispanics; African  Americans; and non-
Hispanic Whites in  an  urban environment. The  majority of the Berkeley  cohort  was comprised of
Mexican Hispanics  from an  agricultural environment. Despite these differences, some patterns have
emerged across these three cohort  studies. Prenatal OP exposures in two  cohorts were  associated with
increased odds of abnormal reflexes in neonates, and in all three cohorts with poorer mental development
in 2- and 3-year-olds and poorer verbal IQ in 3.5-5-year-olds. Increased odds of pervasive developmental
disorder was found in the two cohorts that examined this outcome.


A participant asked  if fruit and vegetable consumption could explain better performance in  children.
Dr. Harley responded that  fruit and  vegetable consumption  was factored into the  model and did  not
account for any differences.

A participant asked about potential confounders in the study. Dr. Harley answered that the study adjusted
for factors that could have a bearing on development and intellect (e.g.,  parental IQ, socioeconomics,

A participant  commented about the findings of a rat study that showed higher  performance levels
associated with CPF exposure and suggested that the researchers examine the higher performing children
in the study to determine if they had higher prenatal exposures.

Cholinesterase Monitoring in Washington State
John Furman, Washington State Department of Labor and Industries

In 2003, the Washington State Department  of Labor and Industries began  an  occupational medical
surveillance  program of agricultural pesticide handlers that measured  cholinesterase (ChE) levels
throughout the pesticide  application  season to  detect overexposure to pesticides and  prevent illness,
increase hazard awareness, identify unsafe  environments, and fix problems.  Symptoms of ChE illness
range from mild to  severe and  include dizziness, blurred vision, nausea, headache, stomach cramps,
diarrhea, hypotension, and seizures; often, many of these symptoms are misdiagnosed.

Acetylcholinesterase  is an enzyme that removes the  chemical  neurotransmitter acetylcholine  from  the
neuronal  synapse.  Humans,  insects,  and  other  species  have  this  basic  acetylcholine   system.
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Cholinesterase-inhibiting pesticides have been developed to kill insects,  but  overexposure in  humans
results in sustained levels of acetylcholine  and overstimulation  of neuronal pathways and eventual
exhaustion of neuronal pathways. Pesticide handlers of Toxicity Class I and II pesticides are monitored
for ChE  levels in red blood cells (RBCs) and serum. Exposure-free baselines are established annually
during periods when handlers have not handled pesticides for at least 30 days. Analyses are conducted
within the same laboratory to  control for  interlaboratory variations. Employees who handle  these
pesticides for more than 30 hours in any 30-day span are tested every 30 days. Employees  may decline
participation but must undergo an informed consent process with a medical provider if they opt out. ChE
depression of 20 percent or more from baseline requires  the  employer to perform a work  practice
evaluation and intervene to reduce any chances of further exposure. Depression of 30 percent or more in
RBC CheE or 40 percent or more in serum ChE requires the employee to be removed from handling until
their levels return to within 20 percent of baseline. In addition  to  monitoring  and  enforcement, the
program  also provides follow-up services  for those with significant ChE depression and  consultation
services to employers to help them reduce  further exposures, reduce possible risk of long-term adverse
health  effects, and decrease take-home exposures. These follow-up efforts  are offered to employees and
employers even if they no longer participate in the program. The program has led to increased knowledge
on the  use of these pesticides, increased hazard awareness, changes in pest management practices, greater
access to medical services, and more informed diagnoses and treatment of pesticide-related illness.
Additionally, the findings of this program are  being integrated into a state-wide  pesticide handler training


A participant requested clarification on the  percentage of employees declining participation with the
program.  Dr. Furman replied that the program is averaging a 12 percent declination rate, and there has
been a sustained participation during the past 3 years.

A participant asked about the change in minimum hours of handling for workers to be tested. Dr. Furman
responded that the  initial  recommendation by the researchers was 30 hours,  but political  intervention
arrived at the 50-hour minimum. No significant correlations were found between handling hours and ChE
depression after 3 years of testing; however, a  legal suit forced the issue, and the hours have been changed
to the initial recommended minimum of 30.

A participant asked if OP pesticides are being  replaced by other pesticides. Dr. Furman answered that part
of the program follow-up procedures capture this information, and a significant number of employers who
were previously engaged in the program have  switched to safer products.

A participant asked about published findings that  demonstrate that these types of interventions lead to
health  outcomes and behavior change. Dr. Furman replied that research reports for each of the 3 years are
posted at http://www.lni.wa.gov/Safety/Topics/AtoZ/Cholinesterase/default.asp.

Biomarkers of Pesticide Exposure:  Lessons for Children in Agricultural Communities
Catherine Karr, University of Washington

Dr. Karr  discussed the utility of ChE testing in clinical practice as a diagnostic tool for identifying
pesticide  poisoning  in  children. Although  significant exposure occurs in  agricultural  workplaces,
playgrounds,  and orchards in agricultural  Pacific Northwest, poisoning  is  not always  considered by
pediatricians. When it is suspected, it is difficult to interpret cholinesterase tests because there often is no
baseline with which to compare it.  Additionally, while cholinesterase tests are useful for diagnosing or
confirming OP  poisoning, there is no test  for detecting  chronic exposure,  which may  have health
implications.  In addition,  while the  symptoms  in classic adult  occupational poisoning  have been
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identified, in children they are not so clear, making diagnoses in children more  difficult. Overexposed
children are much more likely to manifest central nervous system (CNS) symptoms, and very young
children cannot verbalize these symptoms and often present with subtle signs.  Children are more likely to
develop seizures as a result of OP poisoning. The classic hypersecretion (e.g., tearing, diarrhea, urinary
incontinence, sweating)  seen in adults often is not seen in children, and the poisoning is misdiagnosed as
a more common infectious illness, such as flu or gastroenteritis.

Although there is great variability in the normal population, ChE testing still can play a role in the context
of post-exposure followup testing, which can discern if there were significant changes in an individual.
ChE testing is useful for acute  OP poisoning via the  cholinergic pathway,  but  there is evidence that
neurodevelopmental  toxicity can occur  by alternate mechanisms. In vivo embryonic and neonatal rat
models and neuronal rat cell line studies  show effects seen throughout brain regions, including those with
very little cholinergic innervation. Cell loss  and apoptosis occurs immediately  after exposure, neural
deficits  appear later in  adolescent and adult animals, brain  cell numbers are  reduced, and neurite
projections and synaptic communications are disrupted. This  translates into a disruption of signaling
pathways that are very important for normal neurological development in children  and immature animals,
and it is thought that these may underlie some of these observations in the epidemiological studies, such
as effects on performance, attention, and  behavior in humans.

A targeted survey in Washington State was conducted of healthcare providers  and promotoras (lay health
providers) who serve farm families  and farmworkers  in agricultural  regions. Results showed that 49
percent of respondents had received any training on pesticides and health, and 22 percent had received
child-specific information on pesticides and health. Based on these findings, the Washington PEHSU, in
collaboration with the Pacific Northwest Agricultural Safety and Health Center, developed a Web-based
CME product, "OP Pesticides and Child Health: A Primer for Healthcare Providers," which includes
translation of findings from the NIEHS/EPA CEHCs regarding chronic toxicity. Additionally,  in-person
training has been conducted for promotoras who did not show an interest in the Web product.

Dr. Karr ended her presentation  by raising some questions to motivate moving beyond ChE testing and
focusing further on noncholinergic endpoints. She indicated the need for more rapid tests that can be used
in clinical practice to confirm acute exposure to OPs and help provide indication for preventive guidance
to parents. Finally,  she urged participants to begin thinking about OP exposures in children with
neurodevelopmental disabilities (e.g., ADHD  or autism). In addition to potential  etiologic relationships,
these subgroups may be  particularly vulnerable to the toxicity of OP exposure.

Integrated Pest Management in New York City Public Housing
Frederica Perera, Columbia University

Dr.  Perera outlined some of the studies  being conducted  at  the Columbia   Center  for Children's
Environmental Health. Based on high levels of CPF exposure, as measured by plasma concentrations in
mothers and newborns in the Columbia cohort, the researchers instituted: (1)  an educational intervention
with newsletters to members of the cohort and community; (2)  an integrated pest management (IPM)
project; and (3) an effort to develop an early life  reference dose (RfD) of OPs. Levels of use of CPF are
down, following the EPA phaseout for residential use, and the Columbia study recorded a significant drop
in plasma levels of chlorpyrifos in umbilical cord  blood. High prenatal exposure, as measured by elevated
umbilical cord levels, was associated with a decrease in developmental scores  at 3  years using the Bayley
Scales  at age 3, and at 5 years using the  WPPSI. The adverse effect was  observed with the highest
concentrations of CPF occurring before the EPA ban.

The  IPM intervention was formed through a partnership with the NYC Department of Health and Mental
Hygiene and the NYC Housing Authority. It involved professional cleaning to remove food sources and

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cockroach frass (fecal matter) in kitchens and bathrooms of 194 intervention and 129 control apartments.
Following intervention, cockroach populations were decreased, allergens were significantly decreased,
and nearly a 50 percent decrease was seen in the use of bombs and sprays by the IPM group. Effects on
asthma symptoms are being evaluated. Based on these results, the housing authority is expanding the IPM
to other building sites in NYC.

Use of Biomarkers and Physiologically Based Pharmacokinetic (PBPK) Modeling
in Risk Analysis for Developmental Effects of Chlorpyrifos
Robin Whyatt, Columbia University

The newly received EPA Science To Achieve Results grant is designed to use the  exposure response
relationship seen in the Columbia study and, using PBPK modeling, derive an RfD dose for CPF based on
the developmental effects of the maternal dose during  pregnancy. The study approach is enhancing an
already-developed CPF PBPK model to estimate dosimetry during pregnancy. It will incorporate human
interindividual variability in key metabolic parameters, based in part on newer metabolism measurements
in human livers and exposure time pattern data to convert observed CPF levels in cord and maternal blood
to both intake  doses and  internal concentrations of active metabolite for  benchmark modeling.  The
specific measurements to be used from the Columbia study include cord blood levels of CPF at delivery,
maternal  blood levels 1-2 days following delivery,  indoor and personal  air  levels  of CPF, and urinary
levels of a CPF metabolite  (TCPY). These data will  be used with NHANES  data to estimate  what
percentage  of the population in the United States  has detectable levels of CPF in their urine. More
information on this study can be found at http://www.mailman.hs.columbia.edu/ccceh/about.html.


A representative from the New England Asthma Regional Council offered information about research on
the  effectiveness  of IPM,  particularly for homes in low-income populations, that was translated  into
policies and procedures. In conjunction with HUD, the New England Council will be releasing a DVD for
tenants and housing managers on how to use IPM. In addition, over the next few months, the Council will
be releasing a toolkit for policy-makers on how to promote IPM from a policy level  on federal, state, and
local levels and a toolkit for housing managers on how to work with their tenants to put IPM into place
using the Boston  Housing Authority's  successful model. More information can be  found at the New
England Asthma Regional Council Web  Site (http://www.asthmaregionalcouncil.org).

Chair: Maida P. Galvez, Mount Sinai School of Medicine

The goals of this  presentation were to describe phthalate exposure levels in pregnant women, toddlers,
and school age children; identify important sources of exposure in these populations; and understand the
known and potential health outcomes. Based on exposure studies in animals, there is evidence for adverse
birth outcomes, from fetal demise to  modulation of gestational age to adverse impacts on the  male
reproductive  system, including  decreased anogenital distance  in male infants and decreased testicular
function  and fertility. Phthalates are found in a wide range of products,  and there is  potential for
inhalation,  ingestion, and  dermal absorption,  the major pathways  of exposure. The premature  baby
population, which is exposed through medical IV tubing in intensive care units (ICUs), is  considered
highly sensitive to exposures. The potential of phthalates to act as endocrine disrupters is a concern, based
on animal studies and a small but growing body of evidence in human studies.

Legislation banning phthalate use in children's toys was first implemented in the European Union, and
subsequent media reports  raised parental anxiety about  a  number  of items in their homes that may
potentially  expose their children.  Primary pediatric physicians are  in a difficult  position, faced with

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clinical questions that are difficult to answer. Pediatricians receive limited training in CEH in medical
school, have limited knowledge of emerging exposures of concern such as phthalates, and are exposed to
conflicting messages in the media. Dr. Galvez concluded her presentation by introducing the speakers for
this session.

Phthalate Exposures During Pregnancy
Robin Whyatt, Columbia University

The Columbia Center for Children's Environmental Health is conducting research on phthalate exposure
during pregnancy from inner city communities in NYC because it is a universal issue in the United States.
A number of phthalates are endocrine disrupters, including those acting as anti-androgens. Experimental
and epidemiological  evidence  indicates that a number of phthalates are reproductive toxicants and are
associated with malformation in the developing male reproductive tract and other reproductive outcomes.
Recent epidemiologic data indicate that prenatal exposure may modulate the timing of labor.

The specific aims of the  research are to:  (1) characterize phthalate exposures during pregnancy among
NYC African American  and Dominican  women (n =  350); (2) examine effects  of prenatal phthalate
exposures on modulation of gene expression in placental tissue; and (3) examine the effects of prenatal
phthalate exposure on gestational age and fetal growth. This cohort is comprised of 300 mother-newborn
pairs from a larger 725-person cohort and has the same inclusion/exclusion residential criteria as the full
cohort. Phthalates were measured in personal air samples during pregnancy, and biological samples and
gene  expression  were examined. The  conclusions  of this  study are that phthalate  exposures are
widespread among NYC African Americans and Dominicans during pregnancy; phthalates are detected in
85-100 percent of indoor air, personal air and maternal urine samples; indoor air levels appear stable over
time and  are  significantly  correlated with personal air levels in  most cases; there is a  significant
correlation between air and urine levels in two phthalates; and di(2-ethylhexyl)phthalate  (DEHP) expo-
sures may be modulating gestational age.


A participant asked about data on the time of urine collection in relation to when the mothers may have
been using cosmetics. Dr. Whyatt responded that these data have not been analyzed for diurnal variability.

A participant  asked  about air fresheners, because many of them contain phthalates, including those
labeled as "all natural." Dr.  Whyatt indicated that they  collected extensive  questionnaire  data related to
product use, but the data have not been  analyzed  in  relation to  outcome measures.  There is such
variability between products and within brands of products that the questionnaires  may not be capturing
the intended information.

A participant asked if the study will be expanded beyond minority populations. Dr. Whyatt explained that
there are no plans to extend the study beyond the Center's cohort, but phthalate studies are being planned
for the Krakow cohort.

Infant Phthalate Exposures and Potential Developmental Impacts
Sheela Sathyanarayana, University of Washington

The  University of Washington and  Northwest  PEHSU, in concert with the University of Rochester,
examined data from the Study for Future Families, a mother-baby cohort study in Missouri, California,
and Minnesota, to determine whether infant personal care product use was associated with urine pthalate
concentrations and whether maternal  phthalate exposure was associated with developmental outcomes in
infants. The demographic characteristics of the cohort study included 163 infants ages 2-24 months, with

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an even distribution between genders; a racial profile of 80 percent white and 11 percent Hispanic and
Latino; high socioeconomic status; 50 percent of participants from Minnesota and 25 percent each from
Missouri and California; and 91 percent of families reporting health insurance. Infant urine samples were
tested for  detectable concentrations  of nine known  phthalate metabolites,  and all  infants samples
contained at least one detectable phthalate metabolite. More than 80 percent had detectable concentrations
for seven of the metabolites, and over 50 percent showed detectable concentrations for all nine. These
concentrations are similar to or lower than children  6-11 years of age in NHANES data. This may  be
because younger children are not as involved in their environments unless they are walking or crawling;
therefore, most of their exposures come from their parents and diet.  Metabolites were measured to test for
an association with reported use of a variety of baby  products, including baby powder, baby lotion, baby
shampoo, diaper cream, and baby wipes. Infants whose mothers reported using baby lotion, shampoo, and
powder showed increases in urine  phthalate metabolites compared to infants who were not exposed.
Results  of this study suggest that phthalate exposure in infants is widespread, distribution is varied in
infants,  and dermally applied baby  care products may significantly contribute to infant phthalate body
burden.  Reported exposure to baby lotion, baby powder, and baby  shampoo was significantly associated
with increased urinary concentrations of monoethyl  (MEP), monobutyl (MMP), and monoisobutyl, and
the associations were stronger in younger infants.

To determine whether maternal phthalate exposure was associated with developmental outcomes  in
infants,  the researchers examined anogenital distance as a marker in infants because of animal model
evidence that abnormal  anogenital distance is  associated  with  phthalate exposure and genital tract
abnormalities. Exposure in rodents is related to shorter anogenital  distance, impaired testicular descent,
hypospadia, low sperm count, and sometimes testicular tumors. Because short anogenital distance is the
most  important  marker,  the researchers  first created a model estimating the  standard for distance
associated with age and weight. The phthalates associated with the shorter distance included MBP, MEP,
and DEHP phthalate metabolites. Increasing phthalate metabolite  concentrations were associated with
decreasing  anogenital distance in a dose-response manner.  The clinical  implications of these findings
associated exposure with a  shorter anogenital distance and suggest that phthalates may act through  an
endocrine disrupting mechanism to affect hormonal development of genital structures. Researchers also
found an association between increased phthalate metabolite concentrations, decreased testicular descent,
and smaller penile volume, but  these were not  significant.  Further research is needed to determine if
distance is a marker of abnormal male reproductive development in humans.


A participant asked why  an earlier study did not find a metabolite effect. Dr. Sathyanarayana indicated
that the sample  size was not large enough for that study, and that they had used the anogenital index,
which was not an appropriate statistical model for predicting the expected  distance. Based  on feedback to
the earlier  study regarding these issues, the research team  for this study constructed  a new age- and
weight-based model for conducting analyses, but the results of this study have not yet been published.

A participant requested clarification on the hormone involved in these studies and asked if phthalates
could be tested  for with  amniocentesis. Dr. Sathyanarayana explained that the theory is that androgen
decreases overall in utero as a result of exposure, but it is difficult to determine whether it is testosterone
or  some other hormone.  One problem with using  amniocentesis for phthalate detection is that  the
procedure is  not a standard test, and it is  usually carried out on  high-risk pregnancies, decreasing  its
feasibility as an accurate marker for the general population.

A participant asked about the specific components of the baby products that are associated with phthalate
exposures. Dr. Sathyanarayana replied that there is no method to determine the components because there
are no labeling  requirements for chemicals,  which is why studies that identify phthalate-associated

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products are important. California is beginning to mandate disclosure of phthalates and other reproductive
and carcinogenic compounds for products sold in that state. In addition, phthalates are plasticizers that
help bind other compounds together, so it is possible that the manufacturing process may be responsible,
not necessarily the product components.

A participant asked whether synthetic hormone use during pregnancy was controlled for and whether any
of the male  infants had hypospadias or cryptorchidism. Dr. Sathyanarayana responded that the mothers
were asked about hormone use during pregnancy, and all reported no use. None of the  boys had frank
phenotypic abnormalities.

A participant asked whether the U.S. Food and Drug Administration (FDA) had examined this study and
set a maximum level in all  these products. Dr. Sathyanarayana answered that the FDA has evaluated
phthalates previously and has not set any concentration levels, but as the results of this study have not
been published, the FDA  has not  examined the  data. The FDA did  register a warning to health care
providers that concentrations might be high in neonatal ICUs because of IV tubing, but the agency has not
set any mandatory requirements for testing or RfDs. EPA will be undertaking a larger review soon.
Another participant clarified  that the FDA receives advice from a separate industry-run organization but
does not have authority over cosmetic products. The European Union  has banned phthalates in many of
these products, which may be pushing U.S. industries to produce phthalate-free products because they
market to the European Union. One cautionary note regarding phthalate-free products on the market is
that consumer companies still find detectable levels in these products; there must be a higher level of
enforcement at some point.

Inner City Toxicants, Child Growth and Development
Mary Wolff, Mount Sinai School of Medicine

Dr. Wolff mentioned a monograph published by Environmental Health Perspectives in the  1970s that
proved phthalates are not toxic. The issue now is that the levels of phthalates are very high and that some
of the newer generations of bioassays have revealed hormonal effects.  She summarized preliminary data
from the Mt. Sinai birth cohort, a multiracial cohort that included 100 boys and 300 girls from 6-8 years
of age.  The researchers conducted exposure  assessments in mothers during their third trimesters and
outcome measurements of the children. In a cohort of school-age children, levels and variability have
been assessed to determine  feasibility of a single urinary biomarker for these chemicals. Preliminary
results showed exposures similar to the Columbia study for MEP. The mothers had higher levels of some
phthalate metabolites than the Columbia and NHANES cohorts, but were consistent with NHANES for
minorities. Results of temporality studies suggest that some of these biomarkers can be used as predictors
of these metabolites for up to 1 year, and of the three families of chemicals studied, phthalates were the
most reproducible. The Mt. Sinai team also summed groups of phthalates based on molecular weight and
found significant levels of low molecular-weight  phthalates among the minority populations  and higher
molecular weights among whites. Product use questionnaires revealed some borderline associations of the
DEHP metabolites with nail  polish and hair products, but they were not significant  in preliminary data
from a small number of subjects.

Because there currently is much interest in body mass index (BMI) and phthalates because of cross-
sectional data published by NHANES, the researchers examined gestational age. In relation to phthalate
metabolites, the researchers found very weak associations between phthalate exposure and longer
gestation. The researchers currently are evaluating these biomarkers with respect to neurodevelopment.
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Dr. Maida Galvez summarized the  presentations  before opening the  floor to discussion.  Phthalate
exposures are widespread. In this session, evidence was presented from three different cohorts, ranging
from exposures in pregnancy, a particularly vulnerable time period, through early childhood and beyond.
The two cohorts of pregnant women from NYC showed similar levels of exposure, despite the fact that
the populations were very different in racial and ethnic demographics. This is a contrast to exposures in
infancy and  early  childhood  in a predominantly white  cohort, with relatively low exposures when
compared to  the  inner city  populations. The  sources of exposure were  varied, from voluntary use of
products to contamination of indoor air from dust generated from phthalate products.  Through measure-
ment  of the  available biomarkers, there is now limited  evidence from human  studies demonstrating
possible modulation of gestational age and potential impact on anogenital distance. These cohorts will
continue, and effects on body size, particularly BMI and waist-hip ratio; potential associations with
asthma; and other developmental outcomes will be examined. What to tell the parents asking for advice is
a challenging situation, but it is usually best to give them an action item in the face of clinical uncertainty.
Mt. Sinai's Community Outreach  Translational Core developed a pocket guide  to plastics for easy
reference. In the absence of legislation mandating correct labeling of products, these wallet-size cards can
help families identify phthalate-containing products. In general, the plastics to avoid are labeled 3, 6, and
7 for recycling purposes. The CEH  community needs to work together to determine the  best health
messages to relay to families and what policy issues to advocate.

A participant  asked about the Mt. Sinai study participants' access to results. Dr. Wolff explained that
participants were provided with summary data when available on request. Families also would be told
how their levels  compared to the  entire study population on  request, but no individual data  would be
shared with the participants. The researchers were prepared to respond to questions through a potential
collaboration  with the PEHSUs, but no requests have been  received. Study participants did express
concern that  environmental  factors may be related to long-term health  outcomes  such as obesity and
puberty. The  same question was  posed to Dr. Sathyanarayana, who replied  that  study participants
received a one-page handout of the previously published study because the current  study results are not
complete. Dr. Wolffs team will not be submitting individual data, but  its cohort  was educated about
group findings versus individual findings at enrollment. The participants were told that if harm is found
on a group basis, the entire cohort would be notified about those findings and receive information on what
they could do on an individual basis to reduce the exposure.

A participant asked about the issue of potential "sleeper biomarkers" that have been identified  in animal
models but have not been tested in humans. One of the session speakers answered that some studies are
underway, and an issue remains regarding validation involved  in anthropological types of markers, such
as anogenital distance. Some clinicians successfully use the finger ration with certain conditions (autism,
etc.) and the results are very interesting but difficult to measure scientifically. Another participant added
that a new mulitcenter cohort study is underway that uses anogenital distance to examine dysmorphology.

A participant asked for clarification on what the focus was of the pocket guide. Dr. Wolff explained that
the pocket guide identifies plastics  that are associated with phthalates and other chemical exposures from
food packaging. Because dietary sources are considered to be  the major pathway of phthalate  exposure,
the card also includes some information about leaching.

A participant  questioned the usefulness of cautioning the public about phthalate-free products, because
although organic  food contains detectable  levels of pesticides,  it is still considered better because the
levels  are  relatively  lower.  Dr.  Galvez indicated that,  from  the limited consumer product testing,
phthalate-free products do contain relatively lower levels of phthalates, but the study  participants received
cautioning as a process of full disclosure so they could make informed decisions.

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A participant asked, given the relatively small effect size in much of the presented data regarding which
plastic containers or which kind of fragrant-free products to use, where clinicians should put this issue on
the list of priorities when discussing hazards with parents. A session speaker explained that, although
there is no definitive answer regarding humans, it is not a good idea to put phthalates on the bottom of the
priority list in a clinic setting. Animal toxicity data exist, and more studies are planned. Full disclosure
about what is known and what is not known is better than no disclosure.

A participant commented that the benefit of the  CEHCs is that they bring clinicians and the community
together in an academic setting where there is integration of mechanistic and animal scientists. Anogenital
distance studies were prompted by animal studies. Increased collaboration between animal scientists and
human health and environmental researchers will increase opportunities for the CEH community to learn
about biomarkers.  Perhaps  more of the animal models  will be  adapted to human  studies  for more
definitive purposes.

A participant asked if there is a safer substitute for phthalates. A session  speaker explained that there are
other plasticizers and other technologies that do not use a plasticizer, but there are enormous data gaps on
the substitutes.  Nonplasticizers  do not leach as much as plasticizers, so that may be a significant
advantage. Dr. Wolffs team is preparing to submit a paper examining substitutions in the neonatal ICU
because that is where exposures  are higher. The paper examines every substitute to  date and what is
known about them.

Co-Chairs: Kimberly Gray, NIEHS, andLeyla E. McCurdy, National Environmental
Education Foundation

Improving Asthma Outcomes: 2007 NAEPP Guidelines Focus Attention on Education and
Environmental Interventions
David Rowson, U.S. EPA

Mr. Rowson provided  an overview of the 2007 National Asthma Education and Prevention Program
(NAEPP)  Guidelines for the diagnosis  and management of  asthma.  The new guidelines  focus  on
monitoring asthma control as the goal for asthma therapy and  distinguishing between asthma severity and
monitoring asthma control. Treatment should be  initiated based on severity assessment  and then adjusted
based on control. There is a new focus on impairment and risk. Impairment includes the frequency and
intensity  of symptoms, low lung function, and activity  limitations. Future risk  includes the risks of
exacerbation, progressive loss of lung function, or adverse side effects from medications. Clinicians need
to increase the consistency of asthma monitoring, assessment, and care.  There are new modifications to
the step-wise approach to long-term management of asthma. Treatment is partitioned into three different
age groups,  and there  are six specific steps of care that span from intermittent to  severe.  The  new
guidelines incorporate updated approaches to patient education and control of environmental factors and
co-morbid conditions that affect asthma. Finally, there  are modifications to treatment  strategies for
managing and classifying asthma exacerbations. The guidelines are built around a framework  of four
essential  components that include:  (1) assessment and  monitoring  of asthma severity and control;
(2) education for a partnership in asthma care; (3) control of environmental factors and co-morbid
conditions; and (4) medications.

The new guidelines have increased attention on self-management and education of family and individuals
regarding the environment, noting many potential sites  for asthma education and care: homes, schools,
and community  settings.  The guidelines  recommend patients receive  education  in  an integrated,

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multifaceted method in multiple settings. Written action plans are highlighted as a central component of
asthma care,  with a focus  on multicultural ethnic factors and health  literacy to enhance adherence to
physician advice and medication regimens. Provider education  also is highlighted  as an essential
component. Automated assistance helps clinicians to adhere to the guidelines, so these systems are being
put into place to support  them.  The  most important actions patients should take include avoiding
environmental triggers that exacerbate symptoms and cause asthma attacks. The guidelines list potential
triggers  and  a  series of  steps to follow  for  controlling individual  environments.  The  guidelines
recommend testing individuals for sensitivities so that intervention steps  can be  tailored to individual
needs. The guidelines also stress the importance of an active lifestyle. With proper control, exercise
should be possible; if an individual cannot exercise because of symptoms, that should be considered a
benchmark for a change in treatment.

Although asthma rates appear to be steadying nationally, they  remain  at an all-time high, and there  are
significant disparities in morbidity and mortality. Healthy People 2010 goals contain a range of important
indicators; some of those goals are  close to being reached, whereas others are  farther off. The new
guidelines highlight critical areas to  help reach those goals. For instance, the guidelines suggest more
written asthma action plans, increasing adherence with treatment, and controlling for environmental
triggers—all goals ofHP2010.

To support the  delivery of  evidence-based  care  at  the  community level,  EPA is  supporting  the
Communities in Action for Asthma Friendly Environments Network (CAAFE).  Grounded in the results
of the Asthma Health Outcomes Project and conducted by the  University of Michigan, a centerpiece of
CAAFE is the Change Package—a compendium of practical, day-to-day best practices program strategies
that deliver positive health outcomes.  CAAFE is supported by an interactive  Web site developed to
facilitate real-time learning and sharing of best practices, as well as an annual National Asthma Forum.
More   information  on  the   CAAFE  and  the   National   Asthma  Forum  can   be   found  at
http: //www. asthmacommunitynetwork.org.

Prenatal and Early Postnatal Exposures and Asthma Risk—How?
Rachel Miller, Columbia University

Dr. Miller provided a review of mechanistic data that begin to  address the  question of how prenatal and
postnatal  exposures may  affect  asthma  risk. Asthma  is  a  complex disease mediated  by genetic
predisposition, environmental exposures, and host factors (e.g., obesity, psychosocial issues, infections).
Prenatal and  early  postnatal  exposure  (e.g., traffic, diesel, roaches, dust mite allergens, pollens) can
modify asthma risk, and there is evidence that exposure during pregnancy is very important in modifying
or protecting for asthma.  A review of epidemiologic data shows that prenatal  exposure can affect asthma
risk, and the strongest evidence is related to prenatal exposure to  environmental tobacco smoke (ETS).
Prenatal ETS  exposure is associated with  impaired respiratory function, transient wheeze, asthma, and
respiratory infections in infants and young children. Additional exposures during pregnancy that appear to
be associated with an increased risk of asthma include low maternal intake of vitamin E and zinc during
pregnancy, antibiotic use,  and several types of maternal infection. Furthermore, respiratory infection
during pregnancy has been  shown to be an independent factor that may increase later asthma risk. Recent
data also suggest that ambient  air pollution and polycyclic aromatic hydrocarbons may increase risk later
on  in life for  children. Early postnatal exposure to traffic  and combustion-related pollutants has been
associated with both dust mite sensitization and impaired pulmonary function in later childhood. There
may be, however,  other exposures that may help  protect against asthma or wheezing illness.  These
include maternal intake of probiotics during pregnancy, higher birth order, and exposure to dogs and cats
during the first year of life.
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A review of possible relevant mechanisms implicates immune-mediated processes and epigenetics. For
example, multiple studies have shown that cytokine levels differ at birth among those children who may
be more likely to develop  allergy and wheeze. There also is evidence that the fetus can generate an
independent immune  response to proteins  or allergens that the mother  experiences  in  pregnancy.
Epigenetic  changes refer to  those that influence gene expression without any change in the  DNA
sequence. They may  influence  gene expression differentially throughout a lifespan. In  conclusion,
prenatal  and  early postnatal exposures do  impact risk for later  asthma, but more cohort-driven
mechanistic research must be done.

The Center for Childhood Asthma in the Urban Environment
Elizabeth Matsui, Johns Hopkins Hospital

Dr. Matsui, co-investigator for the Center for Childhood Asthma in the Urban Environment, provided
results of some of the  Center's studies. The Center conducted  studies of indoor pollutants and asthma in
Baltimore row homes. Preliminary data showed no differences between asthmatic children and controls
and no differences in  levels of other common allergens. Because mouse allergen levels were higher in
these  homes than in other cities,  the researchers investigated whether the allergens were responsible for
asthma morbidity among children with asthma who were  also mouse sensitized; the results were striking.
Across a multitude of asthma outcomes, there was a significant increase in asthma symptoms in children
who were mouse sensitized and highly exposed. The findings  of this study are an important reminder to
conduct community or regional studies in addition to multicenter studies because local signals can be lost
when combining data from different regions. The researchers examined indoor pollutants in children's
bedrooms; although children with asthma had similar levels of exposure as control children, the causality
of environmental exposure to asthma development cannot be ruled out because prevalence rates of asthma
in this population were between 25 and 30 percent. In addition,  the researchers have not conducted studies
of the same asthmatic children in different environments. Surprisingly, indoor pollutant levels are  much
higher than outdoor levels, and the indoor exposure is likely to play a critical role in the development of
asthma, which is compounded by the fact that children today spend more time indoors than outdoors. The
researchers also looked at indoor particulate  matter (PM) exposure in relation to poorer outcomes  in
children with asthma and found a strong signal for coarse PM. Coarse PM fraction in bedrooms increased
risk in the number of days of symptoms and beta agonist use in children. There were some signals with
fine PM also, but results were not as consistent as results with coarse PM.

Clinical Experience with the Environmental Management of Asthma
and the NAEPP Expert Report 2007
James M. Seltzer, University of California at Irvine

Dr. Seltzer presented an overview of his experiences as an allergist/immunologist caring for children with
asthma and as  a PEHSU Director, who must respond to inquiries from families regarding  symptoms and
the role of environmental  factors  in  allergy and  asthma.  As  a  clinician, he  sees  patients with
environmentally induced  illnesses,  including asthma,  and   other  allergic  disorders.  The  role  of
environmental  factors as precipitants of allergic disease is not always obvious, especially  in children
under 5 years of age or where allergens are only one of several  types of exacerbating factors. This applies
not only to the primary care doctor, but also to the allergist/immunologist  who possesses particular
expertise in determining the spectrum of allergic sensitivity for a given patient. Allergy testing, especially
skin testing, can help identify potentially relevant allergens, whether or not they were suspected from the
medical history. Environmental factors can easily be missed and should be confirmed or ruled out in each
patient with the possibility  of health problems that might be  related to environmental exposures. As  a
PEHSU Director, Dr. Seltzer responds to inquiries from parents, schools, the media, and other entities or
persons  regarding environmental  factors, and the questions typically are  focused on  high-profile
exposures, such as mold and diesel, but not other common exacerbants, such as dust mite or cockroaches.

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He discussed the  significance  of the  assessment of environmental factors in each  clinical case; the
importance of taking a careful,  extensive history; determining if exposures are relevant; and, if relevant,
teaching the  parent and child  how to reduce exposure and to monitor future  exposures and clinical
responses to  exposure reduction. Reducing factors contributing to asthma severity can be accomplished
by environmental  control measures for  clinically relevant precipitants,  such as  reducing sources and
reservoirs of allergens and airway irritants in the child's environment.  Dr. Seltzer also discussed the
hygiene  hypothesis:  early  life  exposures to  certain  allergens  may  provide   protection from the
development of asthma and other allergic disorders later in life. Although early life exposure appears to
have more effect than exposure  later, there are not enough data to recommend early exposure as a method
to reduce future risk. Education is important. Patients and physicians can learn how environmental factors
affect children's health,  thereby improving recognition  of these disorders as well as how to institute
effective environmental control measures. Finally, he outlined the goals of asthma therapy. For control of
asthma  to be  effective,  it must be  recognized, its nature defined, and the  roles of all relevant
environmental  factors  identified  and addressed  for  any given child. With successful  environmental
control, pharmaceutical therapy and, if indicated, immunotherapy (desensitization), the need for clinician
intervention ultimately can be  minimized. Lastly, to be effective, asthma therapy must be practical,
affordable, and convenient.


A participant asked Dr.  Matsui  whether  any composition  studies have  been done to identify PM.
The  Johns Hopkins Children's Center had examined the composition of ambient PM previously, but
composition studies for indoor PM have yet to be performed. Animal particles, however, are much more
readily airborne than insect particles. It will be difficult to measure cockroach PM, because these larger
particles settle quickly and it is difficult to disrupt the dust to become airborne. The other session speakers
contributed to the discussion in regard to outdoor air pollution, including pollen, mold, traffic emissions,
and ozone, and all agreed that individual sensitivities and time of day need to be considered. Ozone levels
generally are highest during middle to late afternoon, and some outdoor molds sporulate at different times
of the day. Additionally, there is difficulty  separating  the effects of indoor pollutants from the effects of
outdoor air pollutants.  Often, allergen and  irritant concentrations are higher indoors. The complexity of
allergen and pollutant exposures, which occur in both indoor and outdoor environments,  combined with
individual differences  in susceptibility to  these exposures, makes it  challenging to  provide guidance
regarding optimal  environmental control measures to patients. In fact, recommendations  in the new
NAEPP guidelines are more  general  than specific  for this  very  reason. It was mentioned that the
guidelines are directed at the delivery of asthma care and what clinicians should do when interacting with
and educating the patient. EPA regulations affect outdoor triggers but do not regulate  indoor exposures,
so patients who are advised to  reduce particular indoor exposures are responsible for implementing the
environmental  control  practices. For those who are not homeowners, appealing to landlords to make
necessary modifications to the home or provide pest extermination is needed. Regarding outdoor exposure
to pollutants, ORD is examining school sites and athletic fields near roadways to better understand this
issue. A session speaker invited participants to become actively engaged in the process of updating the
guidelines, because the guidelines are posted for public comment during development.

A participant asked Dr. Miller for clarification of her lab's work on inhaled allergen and diesel exposure
on DNA methylation and immunoglobulin E (IgE) production in mice.  The question was whether the
exposures in her studies were mixed or single. Dr. Miller responded that the effects on  DNA methylation
and IgE production in mice were measured after combined exposures to the mold Aspergillus and diesel
administered chronically  by inhalation over 3 weeks.

A participant asked  Dr.  Seltzer whether there is a lower boundary  for which to diagnose asthma in
children and what the place of skin testing is in immunotherapy. Dr. Seltzer responded that the diagnosis

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of asthma in a 1- or 2-year-old is problematic, because young children typically have recurring episodes
of wheezing with viral infections. Children in families where other  members have asthma or allergic
disorders are at increased risk of developing asthma or recurring reactive airway disease. Although these
and other risk factors can be identified, in a given child it is more a function of how often symptoms
occur, what they are associated with, and how persistent they are that helps to make the diagnosis. Among
1- and 2-year-olds, although a wheezing child may have asthma, the clinician must be concerned about
other diagnoses associated with recurring wheeze as well. Treatment usually involves a therapeutic trial
of bronchodilator, with or without inhaled steroids delivered by nebulizer or a pediatric mask attached to
a spacer, depending upon age and ability of the child to use a spacer. As far as skin testing, Dr. Seltzer has
tested down to 6 months. Typically, there is less skin reactivity and less IgE in younger children, but
testing can be performed at any time, even at birth.

Co-Chairs: Isaac Pessah, University of California at Davis, and Nigel Fields, U.S. EPA

Neurodevelopment, Autism, and Mercury: Biomarkers and Epidemiologic Approaches
Irva Hertz-Piciotto, University of California at Davis

Dr. Hertz-Piciotto  discussed mercury and its relation to neurodevelopment and autism. The  effects of
mercury are complex, but it is known to cause developmental delays and deficits in the mental, muscular,
visual/spatial, social, and sensory  domains.  Autism is a pervasive developmental  disorder characterized
by deficits in three domains: (1) social interaction, manifested in lack  of eye contact, lack of response to
name, failure to engage in joint attention, and so forth; (2) communications/language, including lack of
language  or odd use of language;  and (3)  repetitive behaviors or restricted interests.  The current
prevalence estimate of autism is about 1 case in 150 individuals and the  ratio  of males to females is 4:1.
There is a strong  genetic component to autism, but environment also may play  a role.  Autism is  a
multifactorial condition with a wide severity curve, yielding high-functioning individuals and individuals
who cannot function independently. Historically,  autism was thought to  be  a result of poor parenting. It
now is  generally accepted that it is  a neuropathologic condition, but this legacy has led  to a general
mistrust of the medical community by parent and advocacy communities. Brain imaging  studies have
shown that facial recognition processing is one of the most affected areas and a hallmark of the condition.
When looking at faces, areas of the brain that are used in typically developing individuals are much less
activated in autistic individuals, and there is no one area of the brain that is affected by autism. Lesions
from  autopsies are  very widespread; this suggests that the insults occur very early in development, most
likely during gestation. The most replicated finding anatomically is the  loss of Purkinje cells.

In the 1950s and 1970s, several high-profile mercury contamination episodes led to mass poisonings in
Iraq and  Minamata  Bay. Children  exposed in utero appeared to  be the most vulnerable.  Severe
impairments, deficits, seizures, abnormal neuronal migration, and disorganized cerebral cortex were seen
in some autopsies.  Studies followed birth cohorts  in communities with high  fish consumption. More than
1,000 mother-child pairs in the Faroe Islands were used to relate development to prenatal exposure, which
was measured through maternal hair, cord blood, and cord tissue levels. The results showed deficits in
attention,  language, memory, and  visual/special  domains in children at 7 years.  Similar findings and
motor deficits were evident  at age 14. The  Seychelles Islands  study found no deficits, and it  has been
difficult to reconcile the conflicting findings. Project VIVA (Venue-Intensive Vaccines for Adults), which
involved maternal hair mercury measurements, controlled for the benefits of fish consumption. Results
clearly  showed the benefits of fish  consumption, and harm from mercury  was measured in a dose-
response fashion. Dental amalgams are a source of an inorganic form of mercury, which is broken down
into the methylated form and travels more easily across the blood-brain barrier. A randomized study
examining children  who received  mercury amalgams  found  no  mental  deficits,  suggesting that

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susceptibility to mercury neurodevelopmental toxicity may be greater when exposure occurs prenatally as
compared with mid-childhood.

Studies regarding the link between mercury and autism are mixed and controversial. Several studies were
conducted on thimerasol, a vaccine preservative  introduced in the 1930s. Thimerasol breaks down into
ethyl mercury and thiosalicylate. It was removed  from many child vaccines in 2002 but remains in some
vaccines (e.g., hepatitis  B virus and influenza). Most studies examining the link between thimerasol and
autism have been in the form of ecologic studies comparing before  and after  removal or introduction.
Very few studies have  individual data, and multiple factors  related  to better  diagnosis make the data
difficult to interpret. Vaccines, however, are not  the only source of mercury. Home sources can include
nasal sprays, contact lens  solutions, ear wax removal products, damaged batteries and light bulbs, and
skin lightening creams.

Dr. Hertz-Piciotto ended her discussion by presenting an overview of the Childhood Autism Risks from
Genetics and the Environment (CHARGE) Study, which is examining the causes and  contributing factors
of childhood autism  risk and the  mechanisms of susceptibility, including those  that are genomic,
immunologic,  and metabolic.  Many possible mechanisms may affect neuronal maturation, regulatory
genes,  immune  signaling,  and  endocrine processes.  She  discussed the catchment area, assessment
measures,  study  design and  laboratory methods,  and  some  preliminary  results.  A multiple linear
regression model was used to predict blood mercury. Preliminary findings showed  that fish consumption
is  predictive of mercury,  and the use of nasal  spray  or ear wax removers or  amalgam fillings was
associated with blood mercury level. There were no associations found with autism.

Future  work will include multivariate  analyses on baby hair locks,  483 newborn blood  spots, and
mothers' hair that  may represent the  prenatal period. Other subsets  will be analyzed regarding  the
heterogeneity, metabolizing genes, and xenobiotics that may affect the  immune system.

Genetic and Social Modifiers in Environmental Neuroepidemiology:  The Role of Context in
Chemical Exposure
Robert Wright, Harvard School of Public Health

Dr. Wright discussed the variance found in studies of chemical  exposure and  health outcomes and
possible  explanations for the different susceptibilities to certain  neurotoxicants. A broad biological
framework for the  reasons children are more biologically susceptible was presented. Fundamentally,
because the CNS is developing, there is ongoing activity (largely absent in adults) on generating cells,
differentiating cells, and cell migration. Finally, those processes that determine  synaptic architecture and
the ability to develop acquired memory are dominant during early childhood. Environmental stimuli drive
whether a given synapse is kept or regresses. This is a form of natural selection and mimics evolution.
Synapses  that serve  an adaptive purpose  are  preferentially  kept, and those  that do not,  regress.
Environmental chemicals may  interrupt these  processes  and  send them down different developmental
pathways.  For example, at low  doses, lead causes neurons  to fire in a stochastic fashion,  thereby
mimicking inappropriate environmental stimuli and the  natural process of natural selection for synapses.
Over time, the resulting  underlying synaptic architecture with prolonged exposure to toxic chemicals will
be less efficient.  Like chemicals, social factors can be  either maladaptive or adaptive.  Neurohormones
such as cortisol are critical to synaptogenesis, and their metabolism changes in response to chronic stress.
Chronic stress, which is a nonchemical toxicant, is known to impair memory and learning capacity.
Because  both chronic stress and lead  share properties that can modify synaptogenesis, the joint or
sequential presence  of lead and stress can be interactive. If instead of being stressful, social factors are
adaptive, animal studies demonstrate they will mitigate  the effects of lead. On the other hand, if they are
maladaptive (i.e., produce stress), they may increase its  toxicity. There may be ways to treat lead toxicity
beyond chelation. In animal  studies, an enriched environment appears to mitigate  the  effects of lead

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poisoning. Following lead poisoning, animals that are socialized perform better than those in isolation
(stress environment). Self-esteem also may modify the effect of lead, as indicated by the results of one
human study. Maternal self-esteem is not  stress, but it may be considered a buffer to chronic stress.
Mothers  with higher self-esteem develop adaptive responses to chronic stress.  Another pilot study in
humans showed that teens exposed to prenatal tobacco smoke and high levels of exposure to violence as
children  (i.e., neurotoxicant and stressor) had worse performance on the Wisconsin Card Sorting Test
than teens with high tobacco smoke exposure and low violence exposure.

Genes also  regulate synaptic formation. The process of synaptogenesis and synaptic pruning is  an
interplay between genetics and the environment. At  least three studies demonstrate that variants in the
apoE4 gene,  which is critical to synaptogenesis, are  associated with  better cognitive performance.
Further, results suggest that the apoE4 gene  variant  might have a protective effect against lead. Blood
manganese also may be a predictor of neurodevelopment, and there is some  evidence that manganese is
neurotoxic. Just as exposure does not occur in a social vacuum, it does not occur in a chemical vacuum.
Some people exposed to lead also  are  exposed to  other chemicals. Animal studies show  that joint
exposure is more neurotoxic than individual exposure to either lead or manganese, and human studies are
being conducted to address this finding as well.

Ongoing work  in  Mexico  City will  examine a  birth  cohort,  in terms  of metal  mixtures and
neurodevelopment and also, with respect to stress as a modifier of lead poisoning, iron-deficiency anemia.
The studies will measure prenatal and postnatal contributions, genetic susceptibility, mixtures  of metals,
and social  modifiers and toxicity. The long-term goals are to identify  those factors  that increase  or
decrease metal toxicity, understand the biology of metal toxicity to  prevent toxicity, and treat toxicity
after it has occurred.

Criminal Behavior as a Late Outcome of Early Exposure to Environmental Lead
Kim Dietrich, University of Cincinnati

Data from previous cross-sectional and ecological studies suggest that there is an association between
exposure to lead and antisocial behaviors, including delinquency and adult criminality, and data from the
Cincinnati Lead Study show an association between prenatal and postnatal exposure and delinquent and
criminal behavior. Lead exposure associated with a higher risk for engaging  in criminal activity is not a
new observation, but it is one that has resurfaced with some recent  epidemiological studies.  One 1996
study examined bone lead levels and the relationship of child scores on the  Achenbach Child Behavior
Checklist. Clinically significant high scores  on  delinquency, aggression, and  attention problems were
measured in those with high bone lead levels.  An observational ecological study examined the correlation
between homicide rates and air lead contamination levels in more than 3,000 counties in the United States
and found a four-fold increase in homicide in counties with  the highest rates of air lead concentrations.
Another study reported a statistically significant relationship between trends in sales of leaded gasoline
and violent crimes.  Strong causal inferences  cannot be made with ecological studies, but the results of
these  studies are very suggestive. Although there are  limitations, these pioneering studies clearly suggest
an association between environmental  lead  exposure  in  childhood and  development  of behavioral

The  Cincinnati Lead Study, funded by  NIEHS  since  1979,  is a prospective longitudinal study that
examines early and late effects of childhood lead exposure on growth, development, and neurobehavioral
outcomes. There  are  many lead paint residues in the catchment area  of  this  cohort study,  and the
researchers have a dense collection of blood lead determinations. Blood is collected prenatally  and every
3 months through the first 6-7 years of life. From questionnaire data from study adolescents, there was a
statistically significant relationship in terms of the number of total  reported delinquent behaviors with
respect to their blood  lead levels.  To  determine relationships of  early exposure  to lead  and adult

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criminality,  criminal arrest records from the State of Ohio were used. Prenatal and 6-year blood lead
levels were  significantly associated with total arrests,  particularly for violent offenses. Lead increases
antisocial behavior through the direct route; it  affects brain  systems that are important in regulating
control. Gene-environment interactions also may play a role. It affects behavior through an indirect route
as well. Early lead exposure is associated with high  rates of school failure and reading  disabilities, and
children who perform poorly in school are more likely to engage in delinquent and criminal activities.
Volumetric  magnetic resonance imaging was used to  examine the brains of study participants.  When
looking at the relationship between blood lead levels in these subjects, there was a significant association
to gray matter  loss in the frontal regions of the brain  (i.e., those areas that are involved in attention,
executive function, and regulation of social behaviors).


A participant asked Dr. Dietrich about separate effects of blood lead at various ages to identify particular
ages that are more important, higher late blood levels as an indicator of sustained exposure, and the
temporal relation across the lifespan. Dr. Dietrich responded that the Cincinnati study  did not address
critical  periods, but there are many intra-individual tracking data.  Blood lead levels  remained fairly
consistent over the  lifespan.  When examining  intra-individual  blood lead levels  in  relation to IQ,
measures of executive function, and criminality, the  later the blood lead, the  more robust the parameter
estimate was in  relationship to late  outcomes.  The higher late  blood levels measured could  be an
accumulated effect, but genetic factors related to excretion or retention  of  lead in the blood may be

A participant asked Dr. Hertz-Piciotto what advice she gives parents regarding consumption of fish.
Dr. Hertz-Piciotto replied that  communication is the key issue with respect to complicated messages.
There is much  variability across fish species, and not all fish have mercury. Several papers show that
many fish species do not have high mercury, so it is best to emphasize consumption of low-mercury fish;
consuming no fish is counterproductive because of the benefits of fish consumption, including during

A participant asked  Dr. Hertz-Piciotto  if her research  collaborators have observed any co-morbidities
between immune responses, mental disorders, and autism spectrum disorders. The participant asked for
comment on the biological pathways by which environmental triggers may be causing some susceptibility
to immunological responses and mental disorders or whether the  environmental triggers are triggering
immune responses that causes brain development to go awry, thus exhibiting the phenotype of autism
spectrum disorders.  Dr. Hertz-Piciotto  replied that,  in regard to  co-morbidities, the research team  is
examining fatty acid screens in children in the CHARGE Study,  and one of the findings is that certain
fatty acids appear to be related to disorders that may be dysregulating. There may be a pathway  where
there is an accumulation of long-chain fatty acids that are not being metabolized to the shorter chain down
the pathway. The team also is attempting to identify additional clinical signs  of these disorders because
they are not always present, indicating that there may  be subclinical issues in a subset of the autism cases.
One of the intriguing findings is of mothers of children with autism who make antibodies to fetal brain
tissue. The CHARGE Study is being  followed up by a prospective study called the MARBLES  Study,
which stands for Markers of Autism Risk in Babies—Learning Early Signs. Mothers of autistic children
are being recruited during or before subsequent pregnancies. Regarding the question of biology versus
environmental factors, all researchers would like to have insight on this issue.

A participant asked Dr. Wright about environmental treatment in humans, the current marker for stress  in
his cohort, and chemical water pollution and exposure  assessment. Dr. Wright explained that he is not
aware  of any prospective human  studies measuring whether the environment changes outcomes, but
cross-sectional  studies have been conducted that examine whether the  social environment modifies

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toxicity of lead or other neurotoxins. Because the brain is developing, there is no reason to think that an
insult that occurs at age  2 necessarily has to  be permanent. His  study  is  utilizing a  variety of
questionnaires to assess stress that examine exposure to violence, negative life events, and perceived
stress measured longitudinally. He also is collecting biological markers of stress, such as salivary cortisol.
By collecting it multiple times over a random day, the diurnal rhythm of mothers during pregnancy and
their children at age 2 can be measured. The NCS  also is measuring  salivary  cortisol at various time
points throughout the day in addition to collecting questionnaire data. Regarding water pollution, not all
forms of lead are bioavailable today but may become bioavailable in the future; therefore, a critical issue
in preparing long-term management plans at contaminated sites, particularly mining sites contaminated
with the relatively inert lead sulfide, is to ensure that nonbioavailables remain so. As an example of what
may develop, he cited the tragedy in Bangladesh in the 1980s. To counter the effects of a diarrhea
epidemic,  shallow wells were dug for cleaner drinking water. But  the digging changed the reducing
conditions in the soil  so that the nonbioavailable form  of arsenic in the soil  changed to a bioavailable
form, which was dispersed in the ground water and poisoned the population. Land and the environment
may be stagnant, but human activity may change the bioavailability of chemicals.

OCTOBER 12,2007

Moderator:  Joanne Rodman, U.S.  EPA

Development Patterns and Children's Health
Tim Torma, U.S. EPA

Mr.  Torma presented background on development  patterns, health, and  the implications of the built
environment. Contemporary community design has a tremendous impact  on  public health,  particularly
children's health, and the  environment. There have been three macro  trends during the last 50 years:
(1) Employment and population growth heavily  favored medium and large metropolitan regions versus
nonmetropolitan areas. (2)  Within  metropolitan  regions,  most growth has occurred in  low-density
development at the fringe of urbanized areas. (3) There has been an emphasis on automobile travel at the
expense of other modes. During the past 20 years, vehicle travel  increased as a result of how and where
populations are  growing, not just because there are more people. Much has been known about this pattern
and its impacts on the environment for a long time. The health impacts of these trends, however, have not
been a focus of attention until recently.

The recent book Urban Sprawl and Public Health reveals that health outcomes are linked with land use
and community design, including air pollution and related illnesses; a  decline in physical activity; obesity
and its attendant diseases; injuries related to auto dependence; threats to water quantity and quality;
mental illnesses; and erosion of social capital. The authors cited the  precautionary principle, "When an
activity  raises the cost of human health, precautionary measures should be taken even  if some  of the
causes are not scientifically proven." Another message from this book  is that urban planners are  public
health officials, whether they realize it  or not. The public health community has been largely absent from
and now needs to engage in the conversation on built environment and development patterns because how
and where building occurs makes a difference.

Mr. Torma's presentation then focused on one particular aspect  of the  built environment—the size and
location of schools. In 1969, 48 percent of children walked to school; in  2002, that percentage dropped to
16 percent. Today, there are far fewer schools than in  the 1930s, but  more students.  Schools are now
bigger, and these "mega-schools" are  not accessible by foot.  Many  states have rules and policies that
mandate or favor large schools; some local districts have even banned walking and biking access, citing

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safety  issues.  Some argue that driving children to school protects them  from predators, but the CDC
performed a study  to determine barriers to walking to school and learned that distance, not "stranger
danger," was the main reason given by parents whose children did not walk to school. Many recently built
residential subdivisions have no sidewalks and are built as pods that require driving to arterial roads to
leave the  neighborhood. There are multiple health implications as a result of the built environment in
general, and unwalkable schools in particular. For public health professionals, school siting decisions are
a logical  place  to  start engaging on the built  environment. Mr. Torma ended  his  presentation by
showcasing The Safe Routes to School Program and the "Regulatory Blueprint for Healthy Community
Design" handout.

Traffic, Trade, Air Pollution and Land Use Decisions
Andrea M. Hricko, University of Southern California

The Children's Environmental Health Center based at the University of Southern California has scientists
who study air pollution.  The Center's Community Outreach and Translation Core  is responsible for
translating science  for the  public,  including policy-makers,  and the  Center's investigators  testify
frequently in  front  of local, state, and federal elected officials..  They also serve  on public scientific
committees and working groups at the local, state, and federal levels, with a focus on ensuring that the
research is delivered to the scientific, transportation, and urban planning committees as it relates to traffic,
trade, air pollution,  and land use decisions. Studies by Center investigators show that children who live
within  500 meters of a freeway have a greater risk of reduced lung function than children who live further
away and that there is a greater probability of asthma in children who live close to busy roads. Local air
pollution exposure has adverse effects on children's lung  function, independent of air quality measures.
Lung function at age 18 is 3-7 percent lower than expected for children  living within 500 meters of a
freeway. Asthma prevalence is greater than 15 percent for children living within 50 meters of a busy road
their entire life, which is nearly double the prevalence  for children living at least  200 meters away,
according to Center studies. Real estate developers need to be informed of these statistics  and should be
encouraged to reconsider their development plans. School budget committees should be informed as well,
but conflict can occur with parents who would prefer to have their children go to a school in their own
neighborhood, even if it is situated close to a freeway, rather than have them be bused to another location.
Some  California schools still  are being built close to  freeways, despite state guidelines  and  laws;
developers cite "overriding considerations" for not following these guidelines and laws. Another potential
conflict includes economics; land is very valuable in certain areas, and the only affordable land may be in
close proximity to freeways.

Ms.  Hricko raised  the  following question:   Should the Federal Highway Administration (FHWA) be
advising state  transportation agencies to consider the latest research findings in their freeway expansion
decisions? Several years ago, EPA issued "hot spot rules" requiring mobile source air toxics analyses, but
currently  FHWA states that it cannot validate the proximity-to-traffic studies  and  is waiting  for an
upcoming Health Effects Institute evaluation.

Dr. Jonathan Samet, in a recent article in Inhalation Toxicology, suggests that: (1) control will require
both reduced emissions and increased separation of people from emissions; (2) there is a need for further
research to refine our understanding  of the health consequences of traffic exposures (and as a basis for
formulating mitigation policies); and (3) a "no-regrets" strategy should be  instituted to reduce exposures
while further evidence is obtained.

Ms. Hricko pointed out that the Los Angeles/Long Beach area is the epicenter for current international
trade and health debates in the United States. The volume of containers  coming through West Coast ports
has increased  dramatically since the  1970s (and U.S. ports have increased their international trade), and
imports continue to grow. Los Angeles ports are the gateway for 40 percent of U.S.  imported products

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today, and imports through these two ports are expected to double or triple by 2030. California suffers the
air and noise pollution and damage to infrastructure, while the rest of country benefits from inexpensive
goods. The  environmental impacts,  however, also travel with the goods. Ships (with unregulated  air
emissions) bring millions of imported containers into California ports, which adds to regional pollution.
Each container then becomes a truck on the freeway or is placed onto a train. Train and truck traffic
creates local problems in communities throughout the country because rail yards often are located in
immediate proximity to homes and schools, increasing the risk of health effects. Traffic, noise, and diesel
pollution increase, and the sense of community is  decreased.  In California, Ms. Hricko pointed out, the
proposed solution to the current congestion is to expand the infrastructure to accommodate three times as
much cargo  and trucks  by  2030. California elected  officials, government staff, and  leaders in the
transportation industry argue that expanding freeway infrastructure will reduce  congestion and improve
air quality.  California bond  money  for infrastructure  projects include budgets for  bridges, rail lines,
freeways, and possibly adding truck-only lanes to the 1-710 Freeway. The governor's current high-priority
projects are a new BNSF rail yard and an expanded Union Pacific rail yard located about 5 miles from the
ports in residential areas.  Community, public health, and environmental groups argue that it would be
better to have rail yards at the ports so that containers are moved directly from ships to trains (and on to
the rest of the country), rather than to have rail yards in  local communities, where residents and school
children have to breathe the diesel exhaust emanating from them.


A participant asked about economic power as the  driving consideration in the school development and
siting. Ms. FIricko responded that there is significant literature that disputes the claim of expected savings
of consolidated schooling. One study showed  that costs are reduced in larger schools  if  costs are
measured per student year, but smaller schools are less expensive if cost per student who graduates is
measured; the issue is complicated. Often public policy dictates spending the money on a stadium in a
prime area versus building a school there.  Segregation is another issue. How is building bigger schools
for integration addressed with well-intentioned public policy?  Smaller neighborhoods and schools tend to
segregate. In the long term, however, economic desegregation needs to be included in public policy.

A participant asked about hot zones and the options for building schools elsewhere when a full 40 percent
of available  land in Los Angeles may be adjacent to major roads and freeways. Ms. Hricko replied that
there are other studies that examine school construction and configurations and that look at siting parking
lots  close to freeways, with the playgrounds and  athletic fields  farther  away (to reduce exposure to
pollutants). Air filtration and air quality management are being tested as other considerations.

A participant  commented on the complexity of planning.  Ms. Hricko responded that when scientists,
physicians, and others in the public health community inject themselves into policy-making, a difference
can be made. It would be a great model for participants to  return to their communities and resolve to go to
a zoning  or planning  meeting  and  offer  health-based information  in  the  planning process, said the
discussant. He asked session speakers to speak more about how these complexities could be incorporated
into  practice.  Mr. Torma explained  that more reports  and research are needed to provide evidence for
take-home messages at these planning  meetings,  but he believes that attending these  meetings with
questions  and concerns can be more  effective than trying to provide all the answers. Merely mentioning
health issues increases considerations from everyone involved in the  planning process; the public health
community  needs  to raise the  questions. Another participant  suggested developing a fact  sheet of
obstacles from the  health care professional standpoint and including possible solutions to those obstacles.
Participants  can bring these fact sheets with them to the zoning meetings as a more effective contribution.

A participant commented about the  fear factor  in  parents, with  regard to children walking to school.
"Stranger danger"  needs to be factored into the equation, whether it is substantiated  by the  statistics or
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not.  Researchers  must be proactive in obtaining and translating these data in a public forum when
discussing school sitings.

One participant asked about cost considerations with building new schools versus updating old ones.
Adaptive reuse is  a great method to manage this issue, especially for buildings that were built in the 1920s
and  1930s and stand for civic pride. Some of these schools are being turned into  lofts instead of being
demolished, but, if possible, the participant suggested, they should be kept as schools. There is a great
amount of literature showing the relative costs of renovating versus replacement. It often is not cheaper to
build new, but to bring the existing schools up to standards, depending on the age and condition of the
schools. Private schools may be more amenable to some of these arguments because they operate under a
different set of constraints and drivers.

A participant asked how lifestyle choices are considered when parents have a host of arguments against
walking to school, including time. Mr. Torma agreed that time is an issue, but people need opportunities
to engage their children; parents could be encouraged to walk their children to school and engage them in
discussions along the way. It is about prioritizing and interacting with children in a manner that does not
occur when driving them or spending time with them at night. A participant suggested  that the global
warming issue is beginning to encourage thinking about these issues.

A participant asked about replacing diesel engines in school buses and if that will change the proximity
issue. A  session speaker responded that there are attempts in many cities to replace diesel buses with
cleaner fuel, although  it may take some time to replace all of the diesel buses. The EPA Clean School Bus
USA Web Site can be  found at http://www.epa.gov/cleanschoolbus.

Marion J. Balsam, NIH

The  NCS is  an interagency, interactive study led by NICHD in partnership with CDC, EPA, and NIEHS.
It was authorized by the Children's Health Act of 2000 to study the effect of the  environment on child
health and  development.  Environments  to  be  studied include  chemical, physical, biological,  and
psychosocial. Gene-environment interaction is an important aspect of the study. The sample will include
100,000 children  from across the United States from before conception through age 21. The goal is to
determine which environmental effects on children are harmful, harmless, or helpful. Another goal is to
find preventable causes of health-related conditions and provide evidence-based  data to guide  children's
health care, as well as health-related policy. Participants will be drawn from 105  sites across the country,
and  40 Study Centers will  perform the  research. The priority is to determine environmental  exposures
(physical, chemical, biological, psychosocial) and their effects on specific outcomes. Priority outcome
areas include: pregnancy outcomes, neurodevelopment and behavior, injury, asthma, obesity, physical
development,  and specific illnesses and disorders. Results from the  core  study are expected to spawn
further research with different research questions.

Adjunct studies will draw upon a subset  of the  parent study participants  and/or their biospecimens or
environmental samples. These will be modular-focused studies, utilizing NCS infrastructure and samples.
Anyone with a good idea can initiate adjunct studies. Specifically, it is expected that many adjunct studies
will  be initiated by government scientists or study center scientists. Independent researchers, research
advocates, and industry can initiate adjunct studies as well. The focus of these studies can be  about any
topic, but there will need to be some mutual benefit to their leveraging the NCS.  The adjunct studies will
rely  on outside funding, not on the core NCS funding source. Reviewers evaluating proposals for adjunct
studies will rate such factors as scientific value to the NCS, public  health importance, and proper fit with
the NCS. Also considered will be the burden on participants regarding time or discomfort, the burden on
the   study infrastructure and logistics, human subject issues for any ethical  or legal  considerations,
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appropriate institutional review board (IRB) review, and proof of funding. A brief electronic preliminary
application is required. After the preliminary application is approved, a full application will be available
for submission. The  review process is aimed at facilitating the timely review of proposals. The NCS
currently is expected to start in July 2008, which is the onset of a 1-year, Vanguard Center pilot year. The
full national study will begin with enrollment 1 year later. Adjunct studies can begin with the full study.
Proposals regarding preconception, delivery, and early infancy  could be submitted soon. Opportunities
will continue to arise for additional research by leveraging the NCS, and adjunct studies will broaden and
enhance the NCS contribution to children's environmental health. More information can be found on the
NCS Web site at http://www.nationalchildrensstudy.gov.


A participant asked whether funding is required prior to applying for adjunct studies. Dr. Balsam replied
that funding is not required, but the application asks about funding plans. After preliminary approval for
adjunct studies pending IRB decisions and so forth, the studies can obtain funding.

A participant asked whether there  will be an opportunity to develop gene expression analysis and arrays
from the NCS.  Dr. Balsam responded that the core protocol is very broad and will include specimen
samples and questionnaires. The NCS will be obtaining, storing, and analyzing the specimens, and the
data will be made publicly available. The research plan is available on the Web site  now, so if others are
planning to do similar studies, they may not want to repeat efforts. The protocol draft is not very specific
about what gene expression analyses are planned, so if participants have specific questions,  they can be
submitted by e-mail to ncs@mail.nih.gov.

A participant asked about the funding status of the NCS. Dr. Balsam answered that the NCS is funded for
Fiscal Year (FY) 2007 and anticipates funding for FY 2008. NCS is funded yearly.

A participant asked  about the  process  for obtaining existing  data and whether it will be similar to
NHANES. Dr. Balsam replied that the policy and procedures dealing with data access currently are being

A participant asked whether any of the people involved with the data warehousing for NHANES also are
involved with the NCS. Dr. Balsam replied yes, the CDC is involved with  sampling,  information
management, and laboratory and repository aspects.

A participant asked whether local sites have to wait  for national  data or whether access is available at the
local level prior to full data.  Dr.  Balsam responded that data distribution currently is being developed.
The NCS anticipates, however, that first access will be to government, followed by study centers, adjunct
studies, and then public use. When communities can have access is part of the process being developed

Chair: Debra Cherry, University of Texas Health Center at Tyler

Dr. Cherry opened the session with a brief overview of the topic: tools for recovery and communicating
risks after hurricanes. The objectives of this panel were to describe the collaborative PEHSU response to
Hurricanes Katrina and Rita, provide experience and feedback from a Gulf Coast pediatrician at ground
zero,  and describe the NIEHS Hurricane Response Portal. Hurricane Katrina was one  of the most
devastating natural calamities to affect the United  States. More than 354,000 Gulf Coast homes were

         The Office of Research and Development's National Center for Environmental Research

            2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
destroyed; more than 200 sewage treatment plants and 140 oil and gas platforms were damaged; and
multiple  health risks increased as a result of rampant mold growth, mountains of debris, widespread
demolition and reconstruction projects, and through exposure to toxicants in temporary housing. The
Tyler, Texas, PEHSU was the closest Center to ground zero and was called to help with communication
issues. The project  involved multidisciplinary collaboration, and  cleanup required  the  expertise of
scientists, engineers, volunteers, health care workers, and safety training professionals.

The potential hazards included returning to home  sites too soon, sludge, structural damage, and lack of
respiratory protection. Joint documents and recommendations for dealing with environmental issues and
returning children to previously flooded areas were created and distributed to officials and parents. The
Center also answered calls from parents through atoll-free line.

Tales from Ground Zero: Hurricane Katrina and Pediatric Environmental Health in
Coastal Mississippi
Scott Needle, Formerly of Bay St. Louis Pediatrics

Dr. Needle joined the workshop by telephone  to share his experiences with the aftermath  of Hurricane
Katrina,  including the  logistical  issues,  the  health  effects, and the  communication  issues that he
encountered, particularly as they related to the formaldehyde problem in Federal Emergency  Management
(FEMA) trailers.

He was in private practice in Bay St. Louis, Mississippi, when the hurricane made landfall. Between 50
and 90 percent of the local  housing was  damaged or destroyed, including his office  and other public
health spaces. Although the medical community was prepared for some of the expected  problems, they
did not  anticipate the  mental health issues  that occurred  including short-term memory problems,
confusion, and disorganization. Trauma was anticipated but not chronic stress.

The Sierra Club found significantly elevated levels of formaldehyde in one FEMA trailer,  which led to
the finding that 29 of 30 trailers had elevated levels. Formaldehyde is a known respiratory irritant and is
classified as a carcinogen; it was found in the particle board in the trailers. The manufacturers voluntarily
had taken it out years before, but the boards were still  circulating. There are no government levels
regulating formaldehyde in travel trailers and  no  standard for levels of safety for children. Dr. Needle
noted that many families reported recurring respiratory problems in their children when they had been in
good health before  staying in the trailers.  FEMA explained that a  small number of cases were being
monitored, and no major problems were anticipated. No government resources were available through the
summer  of 2006 to analyze formaldehyde, but the Sierra  Club still was finding  elevated levels. In
February 2007,  the  media  investigated the  manufacturer of the trailers  and discovered respiratory
problems with the factory workers and particle board sheets that were still wet with formaldehyde. In
May 2007, the CBS Evening News ran a story of results of the 2-month investigation, which prompted the
Department of Homeland Security to contact Dr. Needle to determine how best to study the issue. The
next month, the House Committee on  Oversight and Government Reforms announced that they would
hold hearings  and invited  Dr.  Needle to testify.  FEMA  workers testified that they had voiced
formaldehyde concerns about the trailers as early  as  March 2006. FEMA finally announced  last month
that they are now taking steps to move people out of these trailers. But what about the families still living
in these trailers? The fundamental question remains unanswered:  Is the formaldehyde the cause of the
health problems, and if not, what is? Researchers must work hard to find out. Almost every agency failed
to take ownership and responsibility for public health, and the CDC  cannot just launch an investigation.
The providers on the ground  are the ones providing public health the first few months following a natural
disaster. These providers rely on the experts for advice and need government agencies to listen to their
concerns. Will we be able to handle future problems that weren't anticipated?

         The Office of Research and Development's National Center for Environmental Research

            2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare

NIEHS Environmental Health Sciences Data Resource Portal
Marie Lynn Miranda, Duke University

Dr. Miranda presented satellite imagery of the New Orleans area from pre- and post-Hurricane Katrina
perspectives. These images showed the scale of persistent flooding in an expansive area to help gauge the
potential environmental health effects. The group was tasked with setting up work for the entire Gulf area,
not just New  Orleans. The key health consequences  questions that arose involved mold,  respiratory
health, contaminant transfer,  solid waste management, and  mental health, and the NIEHS  chose to
develop the Hurricane Response Web Portal to build and maintain an extensive data file and archive. This
archive  allows  many different environmental health questions  to be  examined and provides  a
collaborative work space and working tools that allow people from all over the country to work together
on a long-term living resource. Data from the Web  portal can be accessed directly from the NIEHS Web
Site. The portal is user friendly and provides maps and imagery,  query tools, measurement tools, data
manipulation tools, potential contamination sources, water quality information, and sediment information.
There is free and open access to these data. She demonstrated examples of how to make  specific queries
and how to  download data by geographic and other variables and provided navigation instruction. A
customizable research environment and custom reports are available.


A participant recommended a book called One Dead in Attic by Chris Rose for a more information about
how New Orleans has been coping since Hurricane Katrina.

Speaker: Lawrence A. Selzer, The Conservation Fund
Introduction and Discussant:  Howard Frumkin, CDC

Mr. Selzer explained that he wanted to challenge researchers to broaden their investigations to include the
health effects resulting from communing with nature. There is a growing body of evidence pointing to the
benefits of nature, but more data are needed to effect positive change with respect to children's health and
the environment. As the  nation becomes  more  urban and the  demographics continue  to  change,
reconnecting children to nature will be less about bringing them to nature and more about bringing nature
to them. Nature must be brought to children in a manner that makes  sense to them. This  requires a more
strategic vision of reconnecting children and nature; it is a mission that cuts across sector,  status, and
geography. This is the challenge, and leadership is needed to succeed.

One in five American children is considered obese, and one in three with diabetes has the type II form; 25
years ago, doctors did not even have a name for it. Children in the United States now gain three to five
times more weight during the summer than they do during the school year. There are  classes in urban
schools where  as many as one-third of the boys are on Ritalin or similar medicines. Pediatricians do not
see as many broken bones anymore, and one of the most common ailments among children  eight to 18
today is repetitive motion disorder. Fifty  percent of Hispanic boys in this country drop out of school by
the eighth grade. Some states now project their future prison needs based on third grade reading scores. If
this trend continues, the first generation since World War II will exist that will have a shorter life span
than its parents. Sensationalist media coverage and fearful parents have scared children  right out of the
woods while promoting a litigious culture  of fear  that favors safe, regimented sports over imaginative
play outdoors.  This anxiety can feed on itself, and those who watch more  television have more sense of
the potential dangers and less  engagement with their community. The result is the perception that the
outside  has  become more dangerous and thus  the freedom  to  explore  and improvise  is reduced
dramatically. The radius beyond which children are not  allowed to roam has shrunk by 89 percent during

        The Office of Research and Development's National Center for Environmental Research

            2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
the past 20 years. During the past 30 years, children of the digital age have become increasingly alienated
from the natural world with disturbing implications for their physical fitness, their long-term mental and
spiritual health,  and the environment. Young people who  grow up without spending time in nature are
much less likely to be strong champions for the environment when they reach voting age, thereby
jeopardizing the land legacy that the nation has spent the last 200 years setting aside.

Mr. Selzer provided an overview and history of The Conservation Fund, which has protected more than 6
million acres of America's outdoor areas during the past 21 years. Leadership and new ideas, resources,
partners, research, and data are needed urgently. Reconnecting children with nature is the passion of our
time. The National Forum on  Children and Nature is a new  initiative, a collaborative effort launched in
June.  The 2-year  effort is to  identify and implement signature projects across America that serve to
reconnect  children and nature. Individually and  collectively they will be a most powerful form of
advocacy for change,  for a new direction in the products that are made, the services that are delivered in
communities that are built, and the education that is provided.  They will help to elevate this issue to the
highest levels of society  so it  becomes a national priority. Reconnecting children with  nature cannot be
legislated or regulated; it must be done by changing the culture of the country and to do that we need to
better understand the connection between children, nature, and health.

Two examples are being  pursued through the Forum. The first is in the area of technology. The world is
technological, so childrens' attraction to technology must be used to get them outdoors. One idea of the
National Forum is to work with a new  organization  called the Serious Games Initiative,  which was
created by an independent group of game developers who view video games as an opportunity for social
good and achieving social purpose. A national competition to make state-of-the-art technology that has to
be played outdoors is being launched. The next example deals with the built environment, especially how
the environments are built where Americans will live tomorrow.

The modern America of obesity, inactivity, depression, and loss of community has occurred because of
legislation, subsidy, and planning. A subgroup of the  National  Forum consisting of some of the most
progressive developers in the country has been formed. This group is focusing on understanding children
and nature design  elements, identifying best practices, and alternately arriving  at a national certification
standard  for  child-friendly developments.  This  is  the kind of energy  that the  National  Forum is
channeling. The real value of the projects is the opportunity they provide to investigate what happens as a
result. This chance to gather primary data that will help to influence policy and practice across the country
must not be lost. Forum collaborators are building a solid component as part  of each  of these national
projects. They will conduct research on what happens as a result and make these data available.

Beyond the allure of technology, beyond the isolating design of new development, beyond the fear of
stranger danger, there is another fundamental issue that requires  our immediate attention: the increasing
lack of places to be outdoors  and the lack of leadership  at the  federal level to address this issue in a
meaningful way. America loses more than 3  million acres a year  in development and sprawl. The current
administration has proposed twice to permanently terminate the Land and Water Conservation Fund, the
most powerful land protection  program in this country. There also is a crisis in creativity. It is known that
protecting watersheds is one of the methods  by which to assure clean, safe drinking  water, so protecting
the sources of  drinking  water protects public health. It is  known that  air pollution contributes to
cardiovascular disease, respiratory disease, and  allergies. Therefore,  protecting air  quality and  land
protects public health.

Protecting natural landscapes is a powerful form of preventive medicine, but only 5 percent of the money
spent on health  care in the United States is  allocated to preventing  disease and promoting health and a
healthy  lifestyle.  Nature  needs to be  viewed as  the  first  prescription.  People do not  want less
environmental protection; they want smarter  protection that balances economic  and environmental

         The Office of Research and Development's National Center for Environmental Research

            2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
objectives. It is this dynamic that is driving the tremendous force and support of the environment at the
state and local levels. More than 30 billion dollars in just the last 5 years in state and local bond money
were  allocated by taxpayers  to protect open  spaces  across the country,  including natural areas and
neighborhood parks. Recent election results show that a wide  variety of Americans care about these
issues. No one among us wants to be a member of the last generation to pass on to its children the joy of
playing in nature.


A participant asked for clarification about bringing nature to the children versus taking them to nature.
Mr. Selzer responded that redefining what nature means (redesigning alleys to replace lost park land) is
part of this,  but he cited a National Geographic Society program that brings children to national parks.
Children expressed fear of the  dark, of quiet, and of nature. It was too foreign for them to continue
interest in it. Children must be moved along a continuum to help them identify what represents nature in
their own neighborhoods in a manner in which  they can connect and continue with sustained investment.
This improves school performance and increases the number of students who continue to secondary
education; many of them have a lifelong interest in the natural world.

A participant asked about the issue of people who view nature as having a big backyard.  Mr. Selzer
explained that people tend to  show a preference for a house and big yard as a sign of success, comfort,
and quality of life. It is  a cultural issue, but it  has an ecological impact. It  represents a loss of land and
loss of migration and native species. The human health impacts of those kinds of sprawling developments
have just begun to be understood. The impacts  of changing those patterns of development must be
considered and documented through research. For example, only 30 percent of people who live on a golf
course play golf, but they all paid a higher premium to purchase the lots because they like the open green
space. Developers should build  housing developments on open land and charge the higher premium but
they will not because it is an unfamiliar idea. Change must occur slowly, the success  stories must be
highlighted,  and the results documented to effect cultural change.

A participant commented about  the disconnect that she has seen in some of the nature programs; most of
them failed or the children could describe the environment but could not see themselves in it. She asked
for a description of a better way to design these programs. Mr. Selzer explained that what it means to
experience nature must be redefined. Researchers need to come together and promote one curriculum on
environmental education, because there are too many competing factions.  Obesity rates are rising, but
participation in structured sports is the highest it has  even been; therefore, there  is something about
unstructured time and play outdoors that matters. It has to do with engaging with nature first hand.
Environmental education must include being outside in a less structured way.

A participant described a recently convened a group of state and environmental directors that dealt with
the issue of how to collaborate on smart growth and asked what can be done in the early  stages. Mr.
Selzer replied that all that can be achieved with legislation has been achieved, and now the power of the
marketplace is needed to drive things forward. The developers must be encouraged to change.

A participant suggested that participants  should consider running for local office to make  changes. If
researchers sit on local  planning agencies or the  school board, environmentalists and the local health
community will help fund the campaign. Mr. Selzer added that a recent study showed that children who
emerge as leaders in the gray  playgrounds (blacktops) are the most physically mature. The children who
emerge as leaders in a green  playground are the most creative.  Green space is not needed in an urban
setting because sometimes it is not available; some schools put it on their roofs. He described a school of
the future in downtown Manhattan. Regarding running for office, the only thing protecting the land is the
will of the public officials; 20 years from now if the elected  officials do not have a stake in the land, it is

         The Office of Research and Development's National Center for Environmental Research

            2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
in jeopardy, which is why we need to engage children today because it takes a lifetime to build a
commitment like that.

A participant expressed a sense of personal frustration and lack of creativity and mentioned children who
are afraid to go outside because of drive-by shootings. Mr. Selzer agreed that one of the central issues is
safety. He described an initiative called America's Promise, started by Colin Powell. It is an umbrella
organization designed to improve the quality of the lives of the 30 million children who are most at risk in
the United States. One of the  central  directions  is based  on  the  concept of school as the center of
community. Many inner city schools are barren and lacking in programs. Maybe, school can be the place
where education takes place, not just in the classroom, and  where children spend a lot more time. This
will take time, budget, policy, and creativity; and schools as the center of community is the direction in
which this program is headed.

Dr. Frumkin stated that now is the time  to submit proposals through the National Forum on Children and
Nature. Information can be found at http://www.conservationfund.org/children_nature.

William H. Sanders III, U.S. EPA

Mr. Sanders thanked the presenters and expressed his appreciation for their quality  talks. He specially
thanked Mr. Fields and Dr. Frumkin, whose comments  complemented the theme today  of thinking in
broader terms.  The  community is at  a  point of opportunity to think more broadly about CEH to
demonstrate and measure the results. He thanked  participants for engaging the speakers  in each of the
sessions and thanked the planning committee and  coordination teams  for their efforts in bringing about
this workshop. Because this workshop was enlightening  and a great opportunity to connect and discuss
ideas, another workshop may be planed in the future. He anticipates great response to this workshop.

Mr. Sanders adjourned the meeting at  12:30 p.m.
         The Office of Research and Development's National Center for Environmental Research

                2007 Children's  Environmental Health Workshop:
                          Discover, Treat, Prevent, Prepare

                                    Hamilton Crowne Plaza
                                    1001 14th Street, NW
                                      Washington, DC

                                   October 10-13, 2007

                                    Final Participants List
Alicia Aalto
U.S. Environmental Protection Agency

Alan Abelsohn
University of Toronto

Mark Anderson
Denver Health

Bob Axelrad
U.S. Environmental Protection Agency

Daniel Axelrad
U.S. Environmental Protection Agency

Marion Balsam
National Institute of Child Health and Human

Claire L. Barnett
Healthy Schools Network, Inc.

Elizabeth Bayne
ASPH Fellow
U.S. Environmental Protection Agency

Nancy Beaudet
University of Washington

Martha Berger
U.S. Environmental Protection Agency

Liz Blackburn
U.S. Environmental Protection Agency

Cindy Blasko
Magee-Womens Hospital

Joseph Brain
Harvard School of Public Health

Maggie Breville
U.S. Environmental Protection Agency
Margot Brown
ASPH Fellow
U.S. Environmental Protection Agency

Rebecca Brown
U.S. Environmental Protection Agency

Susan Buchanan
University of Illinois at Chicago

Elizabeth Buckley
Pesticide and Toxic Chemical News

Irena Buka
Misericordia Community Hospital

Richard Callan
U.S. Environmental Protection Agency

Kari Casas
University of Texas Health Center at Tyler

Stephanie Chalupka
University of Massachusetts Lowell

Debra Cherry
University of Texas Health Center at Tyler

Gwen Collman
National Institute of Environmental Health Sciences

Tina Maragousis Conley
U.S. Environmental Protection Agency

Nora Conlon
U.S. Environmental Protection Agency

Ted Coopwood
U.S. Environmental Protection Agency

Paula Davis
Association of Occupational and
  Environmental Clinics

Regina De La Cam pa
Canadian Institute of Child Health

Kacee Deener
U.S. Environmental Protection Agency

Dona DeLeon
U.S. Environmental Protection Agency

Kim Dietrich
University of Cincinnati College of Medicine

Darlene Dinkins
U.S. Environmental Protection Agency

Ruth Etzel
Southcentral Foundation

Cathey Falvo
International Society  of Doctors
for the Environment

Elaine Faustman
University of Washington

Nigel  Fields
U.S. Environmental Protection Agency

Michael Firestone
U.S. Environmental Protection Agency

Bettina Fletcher
U.S. Environmental Protection Agency

Brenda Foos
U.S. Environmental Protection Agency

Joel Forman
Mount Sinai School of Medicine

Larry Frisch
Northeastern Ohio Universities College of Medicine

John  Furman
Washington Department of Labor and Industries

Maida P. Galvez
Mount Sinai School of Medicine

Wayne Garfinkel
U.S. Environmental Protection Agency

Robert Geller
Southeast Pediatric Environmental Health
  Specialty Units

Suzanne Giroux
Children's Hospital Boston
Benjamin Gitterman
Mid-Atlantic Center for Children's Health and the

Rose Goldman
Cambridge Health Alliance

Lauren Gordon
ASPH Fellow
U.S. Environmental Protection Agency

Beth Graves
Environmental Council of the States

Kimberly A. Gray
National Institute of Environmental
Health Sciences

William Griffith
Center for Child Environmental Health Risk

Kim Harley
University of California at Berkeley

Michael Hatcher
Agency for Toxic Substances and Disease Registry

Birgit Claus Henn
Harvard School of Public Health

Irva Hertz-Picciotto
University California at Davis

Bette Hileman
American Chemical Society

Mary Hilko
Rocky Mountain Poison and Drug Center

Marianne Hopkins
Harvard School of Public Health

Andrea M. Hricko
University of Southern California

Carolyn Hubbard
U.S. Environmental Protection Agency

Barbara Huggins
The University of Texas Health Center at Tyler

Cathy Hunt
Magee-Womens Hospital

Amaris Johnson
U.S. Environmental Protection Agency

Catherine Karr
University of Washington

Matt Kirby
U.S. Environmental Protection Agency

Katherine Kirkland
Association of Occupational and Environmental

Annette Kirshner
National Institute of Environmental Health Sciences

Susan Laessig
U.S. Environmental Protection Agency

Larry Lowry
The University of Texas Health Center at Tyler

Jenny Lu
Region V Pediatric Environmental Health
 Specialty Unit

Edward Master
U.S. Environmental Protection Agency

Elizabeth Matsui
Johns Hopkins Hospital

Lisa Matthews
Environmental Council of the States

Pamela Maxson
Duke University

Ellen Mazo
Children's Hospital of Pittsburgh

Rob McConnell
University of Southern California

Leyla McCurdy
National Environmental Education Foundation

Regina Milbeck
U.S. Environmental Protection Agency

Mark Miller
University of California at San Francisco

Rachel L. Miller
Columbia Center for Children's Environmental

Marie Lynn Miranda
Duke University

Veronica Monti
Argentine Society of Doctors for the Environment
Ann Naughton
Stroger Hospital

Scott Needle
Bay St. Louis Pediatrics

Tom Neltner
National Center for Healthy Housing

Aaron Niman
Southeast Pediatric Environmental Health
  Specialty Units

Janice Nodvin
Southeast Pediatric Environmental Health
  Specialty Units

Sunghee Oh
U.S. Environmental Protection Agency

Jerome Paulson
Mid-Atlantic Center for Children's Health and the

Devon Payne-Sturges
U.S. Environmental Protection Agency

Cindy Pellegrini
American Academy of Pediatrics

Frederica Perera
Columbia Center for Children's Environmental

Damiris Perez
Mount Sinai School of Medicine

Timothy Phelan
University of Maryland School of Medicine

Pamela Rao
Farmworker Justice

Pat Rizzuto
BNA,  Inc.

Joanne Rodman
U.S. Environmental Protection Agency

David Rowson
U.S. Environmental Protection Agency

Leslie Rubin
Southeast Pediatric Environmental Health
  Specialty Units

William H. Sanders
U.S. Environmental Protection Agency

Jessica Sapienza
National Institutes of Health

Adam Sarvana
Inside Washington Publishers

Sheela Sathyanarayana
University of Washington

Kenneth Schoendorf
Centers for Disease Control and Prevention

James Seltzer
University of California at Irvine

Lawrence A. Selzer
The Conservation Fund

Paula Selzer
U.S. Environmental Protection Agency

Katherine M. Shea
University of North Carolina

Perry Sheffield
Mount Sinai School of Medicine

Martha Shimkin
The Track Group

Adam Spanier
Cincinnati Children's Hospital Medical Center

Marian Stanley
American Chemistry Council

Laurie Stillman
Asthma  Regional Council

Maryann Suero
U.S. Environmental Protection Agency

Oscar Tarrago
Agency for Toxic Substances and Disease Registry

Kevin Teichman
U.S. Environmental Protection Agency

Hugh Tilson
U.S. Environmental Protection Agency

Tim Torma
U.S. Environmental Protection Agency

Whitney Trulove-Cranor
U.S. Environmental Protection Agency

David Turcotte
University of Massachusetts Lowell
Maria Valenti
Greater Boston Physicians for Social Responsibility

Nita Vangeepuram
Mount Sinai School of Medicine

Mary Walker
The University of Kansas Medical Center

Teresa Walker
The University of Texas Health Center at Tyler

Jonathan Weinkle
Children's Hospital of Pittsburgh

Robin Whyatt
Columbia Center for Children's Environmental

Stephen Wilson
University of Cincinnati

Mary Wolff
Mount Sinai School of Medicine

Alan Woolf
Children's Hospital Boston

Robert Wright
Harvard School of Public Health

Margo Young
U.S. Environmental Protection Agency

Contractor Support

Cerena Cantrell
The Scientific Consulting Group,  Inc.

Patrice Pettinato
The Scientific Consulting Group,  Inc.



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Evolution of Biomarkers for Pesticides:
Examples From the Agricultural Setting
           Catherine Karr, MD, PhD
           Director, Northwest PEHSU

            Elaine Faustman, PhD
      Director, Center for Child Environmental
            Health Risks Research

       University of Washington, Seattle, WA
  Focus: Organophosphate Pesticides

Reason # 1: Widespread exposure

Recent decreases in home/garden use
  (regulatory restrictions and phase outs
  based on child health concerns)

Continue to be used heavily in agriculture
                                                              Focus: Organophosphate Pesticides

                                                            Reason # 2: Acute Toxicity

                                                            OP = pesticide type most often implicated in
                                                              symptomatic illness reported
    ILLNESSES. 1996
        Organ iphcsphatas
        Pyrethrins and pyrethroids' -
        Pine oil disinfectants
        HypnchlDrita disinf
        Insect repellents
        Phenol disinfectant;
        Carbamate insecticides
        Organcchlorine insecticides
        Phenoxy herbicides
        Anticoagulant radenticides
        All Other Pesticides
        Total all pesticide^disinfectant
         in. |.i .1 small niiml." r "I • .rr^v.vith unknown fry-.
    '' Rough estimate: include? some veterinary products not classified by chemcal typ
                n '•! \'i'\'' 
             Biologically   Early    Altered
              5rr BSLT r srr
              Dose I   Effect  or Function
    Clinical  Setting Questions

A parent....
I just read the CDC report and I have
  learned that my child may have pesticides
  in her body - what does this mean?  Do I
  need to have my daughter tested?

A colleague....
I am sensitive to drug X, could this affect my
  susceptibility to pesticide""
 Public Health Sector Questions
   Risk Assessment Questions
A public health officer in a rural community...
  Should our healthy family fact sheet include a
  recommendation for choosing organic foods?

  Which populations are most vulnerable to potential
  adverse health outcomes from pesticide exposure?

A federal agency leader....
  Should we have a national medical monitoring program
         tionally exposed agricultural workers?
A policy maker asks....

Has the change in regulation of diazinon and
  chlorpyrifos reduced exposure in at risk

Should regulatory decision making incorporate
  evaluation and protection of the most genetically
  	, _,,	1on?
   Considerations for progress

Stage of validation/utility, limitations,
  knowledge gaps
How to increase the clinical, public health
  and risk assessment relevancy?

                                                                        Key  Issues
   Cholinesterase Testing:
         Pediatric Clinical

          Catherine Karr MD PhD
          University of Washington
Unique clinical diagnostic tool for acute pesticide

Under recognition of OP poisoning in children
  Kids present differently
  Knowledge gap

     T-individual variability
         Cholinesterase Test

Biomarker of biologically active dose

Measures inhibition of Cholinesterase
  enzyme using a blood sample
   Plasma (pseudocholinesterase)
   RBC (acetylcholinesterase)

Surrogate for acetylcholinesterase in the
  nervous system
        Cholinesterase Inhibitors Toxicity
           Effect builds up over time and
          the "Off Switch" gets stuck ON




More likely to have hypotonia & mental status changes
  such as lethargy and coma, seizures

eg. seizure occurrence based on case series:
    adults 2-3%
    children 22-25%

Less likely to have the classic hypersecretion, particularly
  at initial presentation

Often mistaken for viral illness (respiratory infection,

   Under recognition of OP poisoning

                 in children

  In one 1980s case series, the diagnosis was incorrect in 16
    of 20 cases

  In epidemic OP poisoning in midwest, southeast US,
    missing and delayed diagnosis for months to years

  No index of suspicion = no diagnosis
            Training Gap
Health care providers in NW agricultural
  setting caring for farmworker families
Any previous training on pesticides &
  health?              49%
                                                        Child specific info?      22%
        NWPEHSU WebCME
Organophosphate Pesticides and Child Health: a
  primer for health care providers
         Diagnostic Testing
If suspect OP exposure

  Red blood cell (acetylcholinesterase)
  Plasma (pseudocholinesterase)

Certain OPS may selectively inhibit either
  plasma or RBC acetylcholinesterase
     Cholinesterase Activity Depression

   Occurs w/in few minutes or hours

   Effects on plasma enzyme generally persists
     for several days to a few weeks.
   The RBC enzyme activity may take several
     days to reach its minimum and usually
     remains depressed longer, sometimes 1-3
   Cholinesterase Activity Depression:

Great variability in normal general population
  baseline limits usefulness of reference range

Need to interpret in relation to individual's own
  baseline - post exposure follow-up with same
  lab and method
20% increase in  plasma OR 15% increase in
  RBC suggests clinically significant exposure

      Chronic Exposure Toxicity

  Cholinesterase testing is limited to diagnosis
    of clinically significant acute poisoning via
    the cholinergic pathway

  Neurodevelopmental toxicity may occur via
    alternative mechanisms
    Toxicological and epidemiological evidence
     OP Pesticides & Developmental Toxicity:
       Cholinergic-lndependent Mechanism

In vivo evidence (embryonic/neonatal rat models) and in vitro
models (neuronal rat cell lines)

Dosage biologically plausible, below amount needed to
effectively inhibit acetylcholinesterase

Effects seen throughout brain, including regions with little
cholinergic innervation
Cell loss & apoptosis seen i

Neural deficits appear in adc
                               after exposure
    OP Pesticides & Developmental Toxicity:
      Cholinergic-lndependent Mechanism

Several common signaling cascades shown to be effected that
are used in many developmental pathways

   May help explain widespread & delayed-onset OP effects
   during development

   May explain observations in epidemiological cohort studies
     Implications of Non-Cholinergic
        Organophosphate Toxicity
   Child OP exposure toxicity may result from
    non-cholinergic endpoints

  Clinical markers beyond Cholinesterase
    Beyond Cholinesterase testing

  Development of clinical application of urinary
    marker monitoring?

  Confirm acute exposures?
  Identify concerning chronic exposures?
  Influence clinical decision-making?
    Preventive guidance

CMC Biomarker Faustman
           Biomarkers of Pesticide Exposure: Lessons
             for Children in Agricultural Communities
                                                                               Biomarkers for Monitoring Exposure and
                                                                                          Effect in Populations
                           Elaine M. Faustman
                           Bill Griffith
                Examples of Chemicals Applied to
                  Washington State Crops, 2001
               Chemical class
               Organophosphates Apples Azinphos-methyl
                            Potatoes    Ethoprop
               N-Me Carbamates  Apples    carbaryl
                            Potatoes    Aldicarb
               Dithiocarbamate   Apples   Mancozeb
                            Potatoes   Mancozeb
Pounds applied
              Source: "Agricultural Chemical Usage (PCU-BB)" National Agricultural Statistics Service,
              Agricultural Statistics Board, U.S. Department of Agriculture
              (http://jan.mannlib.cornell.edu/reports/nassr/other/pcubbAccessed 05/03)
                                    Agricultural Pesticides: Contributions of
                                 Occupational Factors to Home Contamination
                      Metabolic Scheme for CP
                            Crt3A444lh#twic )

              CNMpynftM O.W*CP*nO*i>
                                                Faustman et at. (2006)
                                   Metabolites of Organophosphate


                                          •  Biomarkers of exposure
                                          •  Nonspecific Diakyl Phosphate
                                            (DAP) metabolites
                                             - Six DAP Metabolites
                                             - Each metabolite can be
                                              produced by multiple OPs
                                             - Divided into two groups
                                                • Dimethyl metabolites
                                                  - DMP, DMTP, DMDTP
                                                • Diethyl metabolites
                                                  - DEP, DETP, DEDTP
                                          •  Specific metabolites
                                             - Chlorpyrifos metabolites
                                                • TCP, DEP, DETP
                                             - Chlorpyrifos-methyl metabolites
                                                • TCP, DMP, DMTP

CMC  Biomarker Faustman
              Metabolites of Organophosphate

                      Selected OPs and DAP metabolites
Diethyl OPs
azinophos methyl
chlorpyrifos methyl
dichlorvos (DDVP)
methyl parathion









 NHANES Data for DMTP in Urine
     Random sample of US Population
Comparison across ages
in 2000-2001
                 Comparison for children
                 f6'11 Vears old) across
            What do these values mean for my
                                                                        Many Values Are Below
                                                                           Limits of Detection
                  Child DETP
                                                                         Quantiles of a log normal distribution
            NHANES Compared to Farmworker Family
                     Data for DMTP in Urine
DMP in Adult Urine: QQ Plots to
Estimate Population Distribution
                                                                          Group of 8 High'

CMC Biomarker Faustman
                                                                                    Distribution of Adult DMTP from year 1:
                                                                                                  Impact of Crop
             Assessing Children's Pesticide Exposure
             via the Take-home Pathway
                            Adult                    Child
                           exposure                  exposure
                                      Car dust
    Urinary metabolites higher in adults who
     worked in pome fruit and their children
   Adult DMTP in Urine
*~  Non-Pome
 Child DMTP in Urine
D  Fruit
D            Fruit
                                                                                         10      100    1000    1      10
                                                                                                 Urinary DMTP |jg/liter
                                                                                                                          100    1000
                                                                                                         Coronado et al., Env. Hlth. Persp., 2004,
                Two longitudinal studies of OP metabolites
              used to estimate within and between variability

              •  Multiple measurements in the same person across time
                permit estimation of both within and between person
                - Within and between person variability treated as a random effect
                  and other variables such as age, gender .residence, season
                  treated as fixed effects
              •  TCP had a low percentage below limits of detection

              •  Measurements below limit of detection (LOD) were
                treated  as being left censored in statistical  analyses
  Predictive Value Positive for Identifying Persons in
  the Upper 10% of the Population
  The predictive value positive is the percent of the population assigned to a group that are
  correctly classified.
                                          Based upon large
                                          within person
                                          variances it will
                                          require a large
                                          number of
                                          samples of
                                          metabolites to
                                          correctly identify
                                          persons in a
                                          population who
                                          are more highly
                                          exposed to CP
                                          and CPM.

CMC  Biomarker Faustman
                Sources of Uncertainty

              - Characterization of Within and Between Person
            Parameter Uncertainty
              - Year-to-Year Variability
              - Observations below Limits of Detection (LOD)
            Model Uncertainty
              - Crop vs. Agricultural Job Task
              - Identification of Highly Exposed Individuals
Biomarkers for Monitoring Exposure and
         Effect in Populations
             Physiologic Based Toxicokinetic
                 Models of CP Metabolism
      Methodology Underlying
     Integrated Framework Tool

 Bayesian Based Mixed Effects Model
  - Correlational structure of a multivariate
   distribution used to estimate correlations
   between pesticide concentrations,
   metabolites, gene expression levels, and
   other variables
  - Markov chain Monte Carlo methods used for
   parameter estimation

        OP Pesticide Exposures
       and Neurodevelopment in
Children from Farmworker Families
                 UC Berkeley
 Center for Children's Environmental Health Research
To estimate sources, pathways and levels of in utero and
postnatal pesticide exposures of children living in an
agricultural community.

To determine the relationship of pesticide exposure and:
     • respiratory disease
                                                                               Characteristics of
                                                                       CHAMACOS Mothers (N=601)
                                                                92%  Spanish-speaking
                                                                85%  born in Mexico; 54% < 5 years in U.S.
                                                                96%  living within 200% of poverty
                                                                44%  6th grade education or less
                                                                44%  worked in agriculture during pregnancy
                                                                84%  other agricultural workers in home

CHAMACOS is a longitudinal birth cohort study
CHAMACOS Biological Specimen Collection
                                 2Y  3>/,Y 5Y  7Y
                                                                                 Delivery 6 M  1Y  2Y 3>/,Y  5Y
             •/   •/   •/
                                                             Paternal Urine
                                                            1 Maternal Blood
                                                             OP Pesticide
                                                                       Organophosphate Pesticide Use
                                                                          in the Salinas Valley, 2001
                                                                               Pounds     Excreted in urine as
                                                                                57,859    Dimethyl (DM)
                                                                                34,224    phosphates
                                                                                17,045    -220,000 Ibs. (42%)
                           Diethyl (DE) phosphate
                  54>945    -199,000 Ibs. (38%)
                  71,725    Other
                  32,669    -104,000 Ibs. (20%)


                                                                              Mary Wolff, Stephanie Engel, Gertrud Berkowitz
                                                                              Mount Sinai School of Medicine
                                                                           Virginia Rauh, Robin Wyatt, Frederica Perera
                                                                           Columbia University
                                                                         Brenda Eskenazi, Kim Harley, Asa Bradman, Amy Marks
                                                                         University of California, Berkeley
        Biomarkers of Prenatal OP
            Pesticide Exposures
Mt. Sinai
                In Urine
 In Blood
         Early Childhood
Neurodevelopmental Outcomes

  Brazelton        Bayley          WPPSI
   Neonatal   6M 1Y  2Y  3Y    3.5Y   5Y
                                                            Berkeley    X
                                                            Mt. Sinai    X
                                                                                          Verbal IQ assessed with

            Early Childhood
      Neurobehavioral Outcomes
                    Child Behavior
                   Checklist (CBCL)
                  2Y    3Y   3.5Y
Mt. Sinai
           Demographics of
          Study Populations
  Non-Hispanic White
 < High school
                  Berkeley   Mt. Sinai  Columbia
Mexican 97   Mex, PR 51  Domi
           Associations with
         7 Brazelton Clusters
  Berkeley     6/7 No associations
  Mt Sinai     6/7 No associations

     Prenatal OPs and Bayley
Psychomotor Development Index
                                                                 Prenatal OPs and Bayley
                                                               Mental Development Index
         Berkeley   Mt. Sinai     Columbia
        (Log10DAPs) (Log10DAPs)  (High v. Low CPF)
6 Months     -0.7
1 Year       -0.6
2 Years      -1.3
                                                           6 Months
          Prenatal OPs and
     Child Behavior Checklist
                    Berkeley    Columbia
                    2Y    3.5Y      3Y
                   Adj OR Adj OR     Adj OR
        Attention Problems  0.8   in prep

Attention Deficit/Hyperactivity  1.3

Pervasive Developmental Disorder  2.3**
                                                                        In summary.
                                                             Three scientifically-rigorous, cohort studies
                                                              — Different populations
                                                               Different exposure levels and sources
                                                               Exposure measured using biomarkers in urine (metabolites)
                                                               and blood (parent compound)
                                                          Despite these differences, some patterns emerge.
            In summary
  Prenatal OP exposure associated with:
    Increased odds of abnormal reflexes in neonates
    Poorer mental development in 2 and 3 year olds
  - Poorer verbal IQ in 3'/2 and 5 year olds
  - Increased odds of pervasive developmental
                                                           Martha Harnly, DHS
                                                                             Intervention and Community Outreach
                                                                             • Abbey Alkon, UCSF
                                                        • Michael Lipsett, DHS
                                                         Janet Macher. DHS

With additional funding from:
                    California Wellness Foundation

Cholinesterase Monitoring in
      Washington State
            John Furman
    Washington State Department of
          Labor & Industries
What Is Cholinesterase (ChE)?

•  Enzyme
•  Present in nerves, brain, and muscle
•  Nervous system's "off" switch
•  If 4 ChE -> ttt acetylcholine -> overstimulation
                            & exhaustion of
                            nervous system
             Thank you to Jonathan H. Siekmann, Ph.D




 Toxicity class I & II products
 • "DANGER" or "WARNING" on the label
   Class I LD 50 of < 50 mg oral or 100 dermal
   Class II LDSOof >50 <500 oral or <1000 dermal
    Pesticide-Related Illness
  -tiredness, weakness, dizziness, nausea,
    blurred vision
  - headache, stomach cramps, sweating,
    drooling, vomiting, tearing, twitching
  - urinating, diarrhea, muscle twitching,
    staggering gait, pinpoint pupils, seizures,
    hypotension, slow heartbeat, breathing
    difficulty, coma , death
   Blood Cholinesterase:

   Convenient Biomarker

 Red Blood Cell (RBC) ChE
 -  Sensitive to Organophosphates
 -  Measures longer-term exposures
 -  Slow recovery
 Serum ChE
 -  Sensitive to most ChE inhibiting pesticides
 -  Measures recent exposures
 -  Rapid recovery

   Normal individual ChE levels vary
  -  Establish exposure-free baseline
  -  Compare periodic samples to baseline

   Different analytical methods exist
  -  Use same laboratory
  -  Use same method

   "Depression" is a decrease in ChE activity in
   periodic sample vs. baseline

Why Monitor Cholinesterase?
   Detect overexposure to pesticides

   Increase hazard awareness
   Identify unsafe environments & fix problems

   Reduce risk of possible long-term adverse
   health effects

   Decrease take-home exposures
 ChE Monitoring in Washington:
    History and Legal Authority

   • 1993 - ChE monitoring recommended
   • 2002-Riosv Washington
   • 2003-WAC 296-307-148 adopted
   • 2004 - 1st year of operation
   • 2006 - Final SAC report
   • 2007 - Move to commercial laboratory
 Who is Tested in Washington?

 Agricultural handlers of Class I and II
 •   Organophosphates
    N-methyl Carbamates

 Exposure threshold:

 2004     >50 hours handling in 30 days
 2005     >30 hours handling in 30 days
        Pesticide Handling

  Agriculture pesticide handling*
  - Mixing, loading transferring applying
  - Disposing of pesticides or pesticide
  - Handling open containers of pesticides
  -Acting as a flagger
  - Cleaning, maintaining equipment that may
    contain pesticide residue
  -Assisting with application

  * See WPS for complete definition
      Handler Participation

   May decline participation
   Employer provided training
   Informed consent process with medical
   Signed declination statement
   Averaged -12% annual declination rate
         Required Actions
•  Work practice investigation
  - >20% depression in either RBC or serum ChE

•  Exposure removal
  ->30% depression in RBC ChE*
  - >40% depression in serum ChE*

*Can return to handling when within 20% of baseline

# Employers

# Baseline tests
# Periodic tests
# Employees with
periodic tests
                  2004    2005  2006   2007*
370     312   244    219
2630    2239  1889   1859
1048     994    692    494
                  580     612   471    362
                 * Preliminary numbers
     Work Site Violations
    Respiratory Protection
    Personal Protective Equipment
    Personal clothing as exposure source
    Pesticide Handler Training
                                                       Work practice
                                                                       2004   2005   2006  2007*
                                                      (17%)   (8%)    (11%)  (13%)
                                     # Medical removals
                                                      (4%)    (2%)   (1%)   (4%)
                                                     119     59     57    62
                                                     (21%)   (10%)   (12%)  (17%)
                                         Increased knowledge
                                         Increased hazard awareness
                                         Training integration
                                         Changes in pest management practices
                                         Improved medical services
                                         Increased stakeholder collaboration

Biomarkers of Pesticide Exposure: Lessons
  for Children in Agricultural Communities
Biomarkers for Monitoring Exposure and
          Effect in Populations
                           Elaine M. Faustman
                           Bill Griffith
     Examples of Chemicals Applied to
       Washington State Crops, 2001
Chemical class

N-Me Carbamates




Pounds applied
   Source: "Agricultural Chemical Usage (PCU-BB)" National Agricultural Statistics Serv
   Agricultural Statistics Board, U.S. Department of Agriculture
     Agricultural Pesticides: Contributions of
  Occupational Factors to Home Contamination
           Metabolic Scheme for CP
                                    Faustman et al. (2006)
    Metabolites of Organophosphate


          • Biomarkers of exposure
          • Nonspecific Diakyl Phosphate
            (DAP) metabolites
             - Six DAP Metabolites
             - Each metabolite can be
               produced by multiple OPs
             - Divided into two groups
                • Dimethyl metabolites
                  - DMP, DMTP, DMDTP
                • Diethyl metabolites
                  - DEP, DETP, DEDTP
          • Specific metabolites
             - Chlorpyrifos metabolites
                • TCP, DEP, DETP
             - Chlorpyrifos-methyl metabolites
                • TCP, DMP, DMTP

   Metabolites of Organophosphate


            Selected OPs and DAP metabolites
Diethyl OPs
Dimethyl OPs
azinophos methyl
chlorpyrifos methyl
methyl parathion


  NHANES Data for DMTP in Urine
       Random sample of US Population

  Comparison across ages   Comparison for children
  in 2000-2001          (6'11 Vears old) across
What do these values mean for my
Samples Collected in Studies of
      Farmworker Families
                                                            Types of samples collected from individuals and
                                                            their children in 3 seasons
                                                             - Urine analyzed for metabolites of OPs—collected 3
                                                               times in 1 week
                                                             - Blood analyzed for parent OPs, metabolites of OPs,
                                                               AChE in RBCs and plasma, genotypes and
                                                               phenotypes of metabolizing enzymes—collected once
                                                             - Buccal Cells analyzed for gene expression—collected
                                                               2 times in 1 week
                                                            Dust is collected from homes and autos in
                                                            thinning and non-spray seasons season and
                                                            analyzed for parent OPs
        Many Values Are Below
           Limits of Detection
                               Baseline Year
                        Child DETP
         Quantiles of a log normal distribution
Q) <»'
Q_ o
C 03
£ 8.
kNES Compared to Farmwo
Data for DMTP in Urin
smparison to Adult Comparison to Childr
rmworkers of Farmworkers (2-5
years old)
5 50 50 0
ill I I
5 50 50 0 500 0
concentration ug/l
rker Family
Data for
farmworkers and
their children
was collected in
two different

   DMP in Adult Urine: QQ Plots to
   Estimate Population Distribution
        Group of 8 Higher
          •:•..',.-;•.'- ; ol'Sr.:; i'l • : :-i :,=;i :_•..-. ;,i
 Distribution of Adult DMTP Metabolite
          1       oono.n.,40. in.,™,,

         Concentration (ug/L)

                       Distribution of Child Urinary DMTP
                           Metabolite Concentrations
Distribution of Adult DMTP from year 1:
            Impact of Crop
                          Baseline Year
                Distribution of Child DMTP from year 1 to year 4
                of CMC study: Impacts of year to year variability
                                                                            Child DMTP

Assessing Children's Pesticide Exposure
via the Take-home Pathway
                 Adult  M        ^^^>  Child
                exposur^^^^       ~^^^ exposure

                            Car dust
                                                                           Assessing Children's Pesticide Exposure
                                                                                    via the Take-home Pathway
                                                                                         xposur^A            j^> expos
                                                                                            %k^^^      ^^^-^
                                                                                                     Car dust

                                                                                          i\      S\
      Azinphos-methyl Take-home Pathway
The dashed black lines that connect the samples illustrate the correlations between the sample
concentrations. The lines are weighted according to the strengths of the correlations. The correlation
statistically significant if the 95% posterior probability intervals (in parentheses) do not include zero.
in adults who
worked in pome fruit and their children
Adult DMTP in Urine

Non-Pome .
Fruit )
/ J

1 10
• '/ '
Child DMTP in Urine


100 1000 1
Urinary DMTP ug / liter
Coronado etc
/» •

• '/ Pome
' / Fruit

10 100 1000
I., Env. Hlth. Persp., 2004, ?006
  Two longitudinal studies of OP metabolites
used to estimate within and between variability

•  Multiple measurements in the same person across time
  permit estimation of both within and between person
   - Within and between person variability treated as a random effect
     and other variables such as age, gender .residence, season
     treated as fixed effects
•  TCP had a low percentage below limits of detection

•  Measurements below limit of detection (LOD) were
  treated as being left censored  in statistical analyses
                                                                           Within and Between Person Distributions for TCP
• Population based

collected at 3
times separated
by 2 days

•90 Children 3-14
yrs old and 263

• Only 20 samples,
8%, below limit of

• Covariates of
gender, age,
residence were
treated as fixed

• NHEXAS data
Shared by John
Quack enboss
                                                                                               NHEXASdata base
                                                                                                                     Within Child
                                                                                        Geometric standard deviation 2.0     .N   Distribution

                                                                                              Urinary TCP (micro-moles/liteo

Within and Between Person Distributions for TCP

                   NHEXAS database

              Maryland: TCP

            Geometric standard deviation= 1.5
• Population
based random
sample collected
over 1 year

• Up to 6
samples per
person, samples
separated by 2

• 79 individuals
and 341

•Only 14
samples, 4%,
below limit of

• Covariates of
gender, age,
season were
treated as fixed
         Geometric standard deviation= 1.8
                                   Between Person

                                     Within Person
                                                                       Predictive Value Positive for Identifying Persons in
                                                                       the Upper 10% of the Population
                                                                       777© predictive value positivt
                                                                       correctly classified.
                                                                                      :s the percent of the population assigned to a group that a
                                    Based upon large
                                    within person
                                    variances it will
                                    require a large
                                    number of
                                    samples of
                                    metabolites to
                                    correctly identify
                                    persons in a
                                    population who
                                    are more highly
                                    exposed to CP
                                    and CPM.
                 Urinary TCP (micro-moles/liteo
                                                                                  Number of Mes
     Sources of Uncertainty

   - Characterization of Within and Between Person
Parameter Uncertainty
   - Year-to-Year Variability
   - Observations below Limits of Detection (LOD)
Model Uncertainty
   - Crop vs. Agricultural Job Task
   - Identification of Highly Exposed Individuals
 Physiologic Based Toxicokinetic
      Models  of CP Metabolism
Integrated  Framework Tool

         Methodology Underlying

       Integrated Framework Tool

   Bayesian Based Mixed Effects Model
    -Correlational structure of a multivariate
      distribution used to estimate correlations
      between pesticide concentrations,
      metabolites, gene expression levels, and
      other variables
    - Markov chain Monte Carlo methods used for
      parameter estimation
                                                         Hypotheses to be Tested

                                                     . Knowing the genotype/phenotype for key genes that metabolize
                                                      CP (biomarkers of susceptibility) will improve prediction of
                                                       - Exposure response
                                                       - At risk individuals in agricultural communities

                                                     . Knowing polymporphisms of oxidant responsive pathways will
                                                      allow us to:
                                                       - Better evaluate the potential for genomic biomarkers of early
                                                         response with OP metabolites of exposure.
                                                       - Better predict relationship of biomarkers of effect (AChE) to
                                                         respond in dose-response manner to the OP exposures in
                                                         adults and children.
                                                       - Better predict whether "omic" biomarkers of disease are
                                                         correlated with OP exposure.
             GO-Quant based
      quantitative pathway analysis
                                                   NIEHS/EPA Center for
                                                   Child Environmental Health Risks Research
                                                                              University of Washington

     Using Markov Chain Monte Carlo
Methods to Estimate Correlation Structure
   above LOD
Replace missing
values by LOD
Univariate Data
Multivariate Data

Phthalates Exposure in Childhood:
     Is there Evidence of Harm?
             Maida P. Galvez, MD, MPH
             Region II PEHSU Director

   Concerns exist about the potential for
   phthalates to act as endocrine disrupters,
   largely based on animal studies and a
   small but growing body of evidence in
   human studies.
                                                      Hormonal effects of phthalates
     Animal Studies
DEHP  fgestational age

DBP   I gestational age

BBP   fbody weight at lactation

DBP,   | serum testosterone

BBP   I Anogenital distance in male infants

MBP   Decreases testicular function
Human Studies



      Phthalates Legislation

   Several countries around the world,
   beginning with the European Union, have
   subsequently banned phthalates in
   children's products.
    Phthalates in the Media

  Widespread media reports on the potential
  harms of fo-x-Sc toys and other children's
  products containing phthalates have
  raised parental anxiety about the impact of
  environmental exposures on their children.

   Primary care  pediatricians
       What Parents Ask
  Faced with clinical questions that are
  difficult to answer:
  - limited medical school training in children's
    environmental health

  - Especially limited knowledge of emerging
    exposures of concern such as phthalates

  -Conflicting messages in the media
Where are phthalates found?
Is this pacifier harmful to my child?
How do I know if toys contain phthalates?
Why was it banned?
What health effects should I look for?
Should I avoid phthalates if I am pregnant?
What substitutes can I use for my child?
      Goals for this  Session

To describe:

• exposure  levels in pregnant women,
  toddlers, and school aged children

• sources of exposure

• known and potential health outcomes
 Is there Evidence of Harm?
Pregnant women in New York City
  Dr. Robin Whyatt
  Columbia University Center for Children's Environmental Health

6-24 month old infants from California, Minnesota, and Missouri
  Dr. Sheela Sathyanarayana
  University of Washington, Seattle, Northwest PEHSU

Pregnant women and 4-8 year old children in New York City
  Dr. Mary Wolff
  Mount Sinai Center for Children's Environmental Health
                                                           Phthalates Exposures are Widespread

                                                                             MEP  MBuPhth MbZPhth MECPP

                                                        NYC Pregnant Women (n=246)  232    37.5

                                                        NYC Pregnant women (n=382)  380

                                                        CA, MI,M02-24mos(n=163)    65

                                                        NYC 6-8 yo girls (n=30)       100

                                                        NYC 6-8 yo boys (n=101)      152

                                                        NYC kids (n=35) 159 samples   166

        Summary of Findings
    Sources are varied
    - Products used
    - Indoor air
    Good biomarkers
    Health outcomes
    -Gestational Age
    -Anogenital Distance
                                   What's the evidence for Phthalates in Cosmetics?

                                    •  EWG report on phthalates in cosmetics
                                    •  Skin Deep Database

                                    •  Safe Cosmetics Fact Sheet
                                    •  12 Ugly Truths Behind the Myth of Cosmetic Safety
                                      Campaign for Safe Cosmetics

                                              How fJm •* ymr bejuty producb*
                                              Skin Dgep  r»
                                               Click h«rt to find Outt
Pocket Guide to Plastics for
     easy reference

  Front of card    Back of card

| Mount Sinai Community
    rteahh Bulletin
  Quit* Guds to Sate Plasl
Key areas for discussion include:

• What is the current evidence for adverse health

• What are the research gaps?
                                      What health messages on phthalates can we
                                      share with families now?
                                                                 What policy issues remain unresolved?
    Barbara Brenner, DrPH (PI)
    Julie Britton, PhD (Co-Pi)
    EunpaChae, MPH
    LuzClaudio, PhD
    Joel Forman, MD
    MaidaGalvez.MD (Co-Pi)
    Jim Godbold, PhD
    Jessica Guttierez
    Philip Landrigan, MD
 Laura Liao, MS
 Ana Mejia
 Kim Morland, PhD
 Arkeyris Richiez
 Susan Teitelbaum, PhD
 Nita Vangeepuram, MD
 Sarah Williams
 Mary Wolff, PhD (PI)
  The Growing Up Healthy CAB:
   -  Children's Aid Society
   -  East Harlem Pediatric/Child Health Subcommittee
   -  Little Sisters of the Assumption
   -  Mount Sinai Pediatrics Associates
   -  Mount Sinai School Based Health
   -  NYCDOHMH's East Harlem District Public Health Office
   -  North General Hospital
   -  Settlement Health

  Susan Resnick at the NYCDOHMH

  Jodi Siskind, Jessica Kobil and Cherita Raines

NIEHS/EPA Children's Environmental Health Research Center
NIEHS/NCI Breast Cancer and the Environment Research Center
(Fox Chase/MSSM)
   - NIEHS Grant #2 P01 ES009584
   - NIEHS and NCI Grant SES0102771

Environmental Protection Agency
   - EPA Grant SR827039
   - EPAGrant#RD831711

Mount Sinai Pediatric Environmental Health Specialty Unit
Agency for Toxic Substances Disease Registry
   - ATU Grant #300014

General Clinical Research Center
   - NCRR Grant SM01-RR-00071

Case Study on Phthalates
Case Study on Phthalates
                                                                             Diiunci PND-2 |m
                     • Control
                                                                            Mil*        Female
Case Study on Phthalates
Case Study on Phthalates
                  Biomarkers of Exposure
                                                                     Phthalate diesters        Phthalate monoesters
Case Study on Phthalates
Case Study on Phthalates
    48 hour personal air 3"  mester      2 week integrated indoor air 32™ week - delivei

Case Study on Phthalates

 Phthalate Diesters In Air  Monoester Metabolites In Urine
Case Study on Phthalates
                                                             Steroid synthesis and
Xenobiotic metabolism

Oxidative stress

Fatty acid transport

Tropho blast
Case Study on Phthalates
Case Study on Phthalates
                                                               Aim 1: Characterize phthalate exposures
                                                               during pregnancy among NYC African
                                                               American and Dominican women.
Case Study on Phthalates
Case Study on Phthalates

Case Study on Phthalates
Case Study on Phthalates



     £  MiBP



     § MEHP


  Aim 2: Examine effects of prenatal phthalate
  exposures on modulation of gene expression
  in placental tissue.
               ]     1000    1500

                Geometric Mean (95% Upper Confiden
Case Study on Phthalates
Case Study on Phthalates
                                                               Aim 3: Examine effects of prenatal phthalate
                                                               exposure on gestational age and fetal growth.
Case Study on Phthalates
Case Study on Phthalates


    Cohort: 163  Infants

       Sex                            Race

       Ages (mo)
                                      Socio-Economic Status
Distribution of Phthalates (mcg/L)
Number of Phthalale Metabolites Found in Infant Urine Samples (N=163)

                                                                                                                  Number of Urine Phthalate Metabolites
                                                                                                      Product Type       Mean Z-s
                                                                                                                           N   %   Subgroup    N   %  Subgroup    N   %
                                                                                                                  <= 8 months  42  (26)   > 8 months  112  (74)  All Infants   154 (100)


   Results  of Regression Analysis
Significant (p-value)
   MBP (0.048)
   MEP (0.005)
   DEHP metabolites
       MEHHP (0.002)
   MMP (0.053)
   MiBP (0.097)

Not Significant
   MBzP (0.826)
* Mixed model including 106 boys and 165 visits
            Clinical Implications
In Rodents
   - At birth: Shorter AGO, impaired testicular descent,
     hypos padias
    i Later Low sperm count, rarely testicular tumors

Our Study of Humans Suggests
   • At birth: Shorter AGO (some, but most NS, decrease in
     testicular descent, smaller penile volume)

           Future studies needed to determine
              clinical correlates in humans
                                              U Rochester
                                              Shanna Swan
                                              Fan Liu

                                              U Washington
                                              Catherine Karr
                                              Paula Lozano
                                              Robin Kruse,
                                              Sara Stewart, Lynn Teague

                                              Christina Wang, Cathy Mao
                                                                                                    Dana Barr.Antonia Calafat
Jim Overstreet, Charlene Brazil
                                                                        U Copenhagen
                                                                        Katharina Main
Bruce Redmon, Chris Ternand

                                                      "AL. HEALTH &
                        Urinary phthalate metabolites in 3 populations
                                                                                  MEP, adjusted GM ug/gC
                                                                                                              MCPP, adjusted GM ug/gC
    *BPA: - with use of drink containers (p= **, wrong direction)
    *BPA:  no correlation with "foods that come in cans"
    *BP3: +• with use of sunscreen (p<.001)
Phytoestrogens:   0.17 (Dai)      0.33 (Gen)
Phenols:          0.35 (BPA)

    EHigh-molecular weight
                                            ELow-molecular weight
                                                                                                              ZHigh-molecular weight
                                                                                                                                                          ZLow-molecular weight



           Quartilas of low-MWP
Maternal  pre- pregnancy BMI  (kg/m2)
    predicted from phthalate and
  creatinine biomarkers Children's
Environmental Health Study,  1998-
                                                                                              Adjusted for race, infant sex, gestational age, In-creatinine; restricted to samples with
                                                                                              creatinine >20 mg/dL. Rs with creat = .49 (Hi) .42 (DEHP .39 (Lo)


          Quartiles ofhiah-MWP


  Improving Asthma Outcomes:
  2007 NAEPP Guidelines focus attention on
  education and environmental interventions
                                  David Rowson, Director
                            Center for Asthma and Schools
                       US EPA Indoor Environments Division
   Overview of the 2007 NAEPP Guidelines for the
   Diagnosis and Management of Asthma
   Highlight Guidelines recommendations for patient
   education and control of environmental factors
   Introduce EPA Initiative to accelerate adoption of
   best practices
National Guidelines for the Diagnosis and
Management of Asthma
National Guidelines for the Diagnosis and
Management of Asthma

   New focus on monitoring asthma control as the goal for asthma
   therapy and distinguishing between classifying asthma severity and
   monitoring asthma control.
   New focus on impairment and risk as the two key domains of
   severity and control, and multiple measures for assessment.
•  Modifications in the stepwise approach to Managing Asthma Long
   New emphasis on multifaceted approaches to patient education and
   control of environmental factors and comorbid conditions that affect
•  Modifications to treatment strategies for managing asthma
Guidelines Frame-work: 4 Essential Components
of Asthma Care
  Assess and Monitor Asthma Severity and
  Education for a Partnership in Asthma Care
  Control of Environmental Factors and Comorbid
Educating patients, families, and providers

Education for a Partnership in Asthma Care:
Self-management education is essential, should be integrated into
  all aspects of asthma care, and requires repetition and

  Patient education
  a Many potential sites/points of care outside office setting
  a Written asthma action plan emphasizes both daily management
    and worsening asthma
  a Attention to cultural, ethnic factors and health literacy
  Provider education
  a systems-based interventions and
  a effective clinician education programs

Multi-faceted approach to control environmental

Multi-faceted approach to control environmental

   Reducing exposures to inhalant indoor allergens and irritants improves
   asthma control
   a Determine exposures and sensitivities—use skin testing or in vitro testing for
     persistent asthma
   a Consider allergen immunotherapy for persistent asthma and clear, consistent
   Multi-faceted approach is most effective
                                                                            a  Tobacco Smoke
                                                                            a  Dust Mites
                                                                            a  Animal Dander
                                                                            a  Cockroach
                                                                            a  Indoor Mold
                                                                            a  Pollen and Outdoor Mold
                               a Smoke, Strong Odors,
                                 Sprays, Formaldehyde,
                               a Vacuum Cleaning
                               a Exercise or Sports
Asthma in the US
   20 M, including 6.3M kids
   a 2M ER visits
   a 14M missed school days
   Some National indicators leveling off, but at all-time highs
   a Prevalence, ER visits, hospitalizations
   Important disparities in morbidity and mortality continue
   a Children and the elderly
   a African Americans, Native Americans, Hispanics
   $16.1 B in annual costs
   a direct health care costs, e.g. physician services-$11.6 B
   a indirect costs, e.g. school/work absence, mortality -$4.5 B

ealthy People 2010: How are we doing?
Healthy People 2010
on'hoTto^th'em^raprrly ^'^ mstmctl0n

Written asthma management plan from their HC
schoTan'd work environments1 ^ ^^
Formal patient education, including information

Driving Improvements in Asthma Care through

Increased Patient Education/Control of Triggers
  Health Care Provider outcomes
  a  Increasing numbers of patients receiving
       written asthma management plans
       assistance with trigger avoidance

  a  -30% taking essential environmental control actions

•  Health Plan Results
  a  Widespread promotion of guidelines to providers
  a  Increased support for education/environmental interventions
  a  Business case is becoming more evident
Accelerating progress through Community-based
asthma care

  Asthma Health Outcomes Project
  a  Identified program elements linked to health
  Change Package of Successful Strategies
  a  Compendium of field tested actions
  Network of programs driving toward best
  practices and outcomes
  a  www.asthmacommunitynetwork.org

   Cambridge Health Alliance
 Collaborations & Partnerships
 • School System
 • Department of Public Health
 • Advocacy with city government
 and politicians
Integrated Health
Care Services
• Registry as a "connector"
• EMR supporting "best pra
• Performance outcomes linked to
• Educated clinical care teams
on evidence-based guidelines (NHLBI)
   Strong Community Ties
   • Linkages with School Nurses
   • Chief of Pediatrics is co-chair of
   Healthy Children's Taskforce,
   Cambridge, MA
Tailored Environmental
•Asthma Action Plan for each child
• Referral to Healthy Homes Program
(RN home assessment, patient
education, and home supplies
                       Committed Program Champions
                       • Providers, nurses, and staff at practice site:
                       • CEO and Senior Leaders
                       • Chief of Pediatrics and Family Medicine
                       •Ambulatory Administration
                       • Performance Improvement Department
                       • IT Department

Communities in Action Network
Reduce ED Visits
Reduce Hospitalizations
Increase Symptom-Free Days
Patients receiving Education
Patients receiving Assistance to
Assess/Reduce Triggers
HP 2010 Target
30% - 50%
(15-80 per 10,000)
38% - 45%
(8-25 per 1 0,000)
>10 per 14 days
Best in Class
50% - 75%
50% - 80%
10.4 days in a row

   Communities in Action Network
                                           Mobilizing 1000 Communities to deliver quality
                                           asthma care

  Looking Ahead
     Educate clinicians and others in health care community
     to follow new NAEPP Guidelines
     Clinicians collaborate with community resources to
     deliver comprehensive care addressing all 4 components
     of asthma care
     Your programs are leaders in understanding effective
     Join the Communities in Action Network
     Join us May 1-2 at  the 3rd National Asthma  Forum

 Prenatal and early postnatal
 exposures and asthma risk-
        Rachel L. Miller M.D., FAAAAI
Columbia Center for Children's Environmental Health
           Columbia University
           sntal Health Workshop: Discover, Treat, I
  Asthma is a complex disease

Mediated by
-genetic predisposition
-environmental exposures
- host factors eg obesity, psychosocial
- infections
      Epidemiological support:
     Prenatal exposure to ETS

 ETS is associated with
 - impaired respiratory function
 -transient wheeze,asthma, and/or
   respiratory infections in infants, young
   children, and adolescents
  Additional prenatal exposures

Increase asthma risk?
- Low maternal intake of vitamin E, zinc
-Use of antibiotics
- Respiratory infections during pregnancy
-Ambient air pollution eg PAHs
Decrease asthma risk?
- Probiotics
- Multiple pregnancies
                     •pidemiology 2006;17:138-144

      Epidemiological support.
     Early postnatal exposures

Dust mite allergen during infancy
 - determinant for later childhood asthma
Dog, cat allergen
 - associated with protection from later childhood
Combustion-related pollutants
 - associated with later childhood sensitization to
  dust mite
 - reduction in FEV.,
       Prenatal PAH,  postnatal  ETS and
           respiratory score (CCCEH)
           Analysis for Main Effects
                                   Analysis for Interactions
12 months
         Intercept     0.68
                Sporik R et. al. NEngl J/Wed1990;323:502-507
                Remes et. al. J of Allergy and Clinical Immu,
                Ponsonbvet. al. Clin Exo Allerav 2001:31:1!

                                                                 Epigenetic-mediated mechanisms

                                                                 Heritable changes* in gene expression
                                                                 that occur in the absence of alterations
                                                                 in DMA sequences
                                                                                    ' at least between cells
          Epigenetic regulation
DMA methylation
 - covalent addition of a methyl group to cytosines in CpG
Chromatin packaging of DMA via post-translational
modifications of histones
 - egs. acetylation,methylation,phosphorylation
Believed to occur predominantly prenatally and
shortly after birth

May influence gene expression differentially
throughout lifespan
   Eg: T helper cell differentiation
Proallergic IL-4 production and Th2 differentiation
 - demethylation of sites at the prox promoter and
  conserved intronic regulatory element (CIRE) in 1st
  intron of the IL-4 gene
 - hypermethylation of sites in the counterregulatory IFNy
Th1 differentiation
 - methylation of a highly conserved DNasel-
  hypersensitive region at the 3' end of the IL-4 locus

In vivo study of methylation of IL4 gene
      in asthma-like mouse models
               AspAg    Dl
              Collect CD4+ cells
             Isolate genomlc DMA
             Bisulfite conversion
              PCR amplification
         Pyrosequence of IL4, IFNy gene:
           Quantify methylation level
 Methylation profiling using methylation
    sensitive restriction fingerprinting

  •  Study population/samples: CCCEH cord
    PAH exposure
    - high prenatal PAH exposure: highest
      quartile prenatal air PAHs/high PAH-DNA
    - low exposure: lowest quartile PAHs/low
      PAH-DNA adducts

  Prenatal and early postnatal exposures impact risk
  for later asthma
  Both immune-mediated and epigenetically-
  regulated mechanisms likely contribute

  Much more cohort-driven mechanistic research
  needed to assess:
   - dose of specific exposures
   - time periods of increased susceptibility
   - interactions btw genetics and epigenetics
Frederica Pererc
Graham Barr
Chris Espino
Ginger Chew
Inge Goldstein
Alina Johnson
Manisha Ballane
Andria Reyes
Umaima Al-alem
Cynthia Lendor
Kathleen Moors
Rachel Miller
Rafael Narvaez
Matt Perzanowski
 University of Cincinnati: S. M. Ho, V\
 CDC: D. Barr, T. Bernert, E. Gunter,
 Schleicher, L. Needham, D. Pascal,
                                                                                                        Jullie Herbstrr
                                                                                                        Susan Edwe
                 Jmming Liu
                 Deliang Tang
The CCCEH  research has been made possible by funding
    i Star grants: R-82860901; R-827027; RD-83209601

The Center for Childhood Asthma in the
           Urban Environment
              Elizabeth Matsui, MD MHS
             Patrick Breysse, PhD, Director
          Gregory Diette, MD MHS, Deputy Director
              Johns Hopkins University
                                                  Bedroom Cockroach
                                                             Asthma    Control
                                                                    Diette G etal, Env Health Perspective, In Press
3500 n
         Bedroom Settled Dust
            Dust  Dog   Cat  Mouse
                Diette G etal, Env Health Perspective, In Press
Recent Asthma Symptoms
Medication use
3 -,
Matsui E eta
& Rescue

I '

ted for age, sex, atopy, cockroach sensitization and
re, public health insurance, and study visit
, Ann Allergy Asthma Immunol. 2006 Oct;97(4):51 4-20.
Asthma-related Health Care Use


• Hospitalization
Adjusted OR:
69.9 (5.8-838.9)
• 9/10
occurred among
exposure group
UD Visit ED Visit
djusted for age, sex, atopy, cockroach sensitization and exposure,
blic health insurance, and study visit
                                                          Bedroom Air Pollutants
                                                            Diette G etal, Env Health Perspective, In Press
                                                           PM2.5   PM10   N02   Ozone

Distribution of Indoor PM in Children's Bedrooms
 Figure 2. Distribution of Indoor and Ambient Fine and Coarse PM
 Boxplots display indoor and ambient fine and coarse PM.  Indoor PM concentrations were significantly higher than
 ambient. The red dashed line demonstrates the EPA annual limit for ambient PM25 Over 75% of homes had indoor PM
 concentrations that exceeded this limit.
                                 Indoor Coarse   Ambient Coarse
                                       Extreme outliers not shown
      - EPA
      - NIEHS
      - Peyton Eggleston
      - Patrick Breysse
      - Gregory Diette
      - Nadia Hansel
      - Elizabeth Matsui
      - Francesca Dominici
      - Timothy Buckley
 - Study Staff
 - Laboratory Staff
 - Exposure Assessment
 - Data Management Core
Community Advisory
 - Adrian Mosley (chair)
Indoor PM Exposure and Asthma Morbidity
Cough/wheeze/ chest
Slow/stop activities
Limited speech from
Nocturnal Symptoms
Symptoms with
Beta agonist use
Coarse PM
(per 10 ug/m3)
*Adjustedfor age, gender, race, socioeconom
(per 10 ug/m3)
c status Presented ATS 2007

    Clinical Experience with  the
   invironmental  Management  ol
-thma & NAEPP Expert Report 2007
              James M Seltzer, MD

           Clinical Professor of Medicine

           University of California, Irvine

               School of Medicine


     Pediatric Environmental Health Specialty Unit,

               US EPA Region IX
                                         Three Questions

                            What is my experience as an
                            allergist/immunologist caring for children with
                            asthma as this disease relates to environmental
                            What is my experience as a PEHSU director
                            responding to inquiries from children with
                            asthma, their parents, and other involved
                            entities/persons regarding environmental
                            What is the significance of the new asthma
                            guidelines for the clinician in his office?
                             - Primary care
                             - Specialist
        4 essential com^
               asthma care
     Assessment and monitoring

        Relevant or potentially relevant environmental exposures

        Compliance with exposure reduction

     •  Response to exposure reduction

     •  Monitoring of future exposures

      Controlling factors contributing to asthma severity

     •  Environmental factor exposure reduction and minimization
        (or possibly, exposure enhancement) - "environmental
        control measures"

     •  Co-morbid conditions
                                                              October 11, 2008
                                                                                 James M Seltzer, MD

        4 essential com^
               asthma care
     armacologic and immunologic treatment - stepped
      Anti-inflammatory "controller" medications still the mainstay for
      asthma control
      Specific immunotherapy can reduce the risk of future asthma
4. Patient and physician education
   •  Asthma mechanisms, including effect of environmental
      •  Medication use
      •  Relevant environmental control measures
   •  Written action plan
                                                                  October 11, 2008
                                                                                      James H Seltzer, HD
                                                                            jals of asthma thei
                                                                          ctive asthma control - define it
                                                                          imal therapeutic regimen, e.g., number of
                                                                         idications for asthma and other allergic
                                                                      Minimize need for health care professional
                                                                      intervention, e.g., doctor's office, E.D., hospital
                                                                      Practical,  i.e., doable


  Neurodevelopment, Autism, and
       Mercury: Biomarkers and
      Epidemiologic Approaches
         University of California Davis,
                M.I.N.D. Institute

  Literature on:
   — Hg & Neurodevelopment
   - Hg & Autism: vaccines
   - Hg & Autism: non-vaccine sources
  UC Davis CCEH: The CHARGE Study
   - Goals, methods & results for Blood Hg
  Discussion & Next steps
            What is Autism?
  Developmental delay or deficits
  Mental or Cognitive:
Pervasive developmental disorder defined as
  characterized by three behavioral domains:
   — Executive function
  Sensory deficits
  Social: autism
   ^Deficits in social interaction
   >Communication: Language impairment/delay or
    unusual speech patterns
   > Repetitive behaviors and/or restricted interests
           Facts about Autism
  Male: female ratio is 4
  1 in 150 (=60-70 per 10,000)         |
> Strong genetic component           1
  > 60-90% concordance: monozygotic twins
 * Multifactorial
 * Wide variation in severity, trajectory
  Historically attributed to 'bad parenting'
, Now known to have a neurobiologic basis:
  aberrant brain development
      Neural Substrate of Autism

  Anatomical, electrophysiologic, MRI
  fMRI: esp face processing
  Highly diffuse throughout the brain:
   — Cerebellum
   - Hippocampus
   - Amygdala
   — Cerebral cortex
                => early insult
                                                              Purkinje cell los

   Mercury and Neurodevelopment

Mercury: food contamination episodes
• 1953-1961 Minimata, Japan, chronic
• 1970'slraq
   - in utero exposure ~ mental retardation, physical
    impairments, seizures
   - autopsies showed abnormal neuronal migration,
    disorganized cerebral cortex
    Mercury and Neurodevelopment
Chronic Hg intake via fish consumption - (lower levels)
 * Faroe Islands (n~900) Grandjean et al 1997, Debes 2006
prenatal exposure: maternal hair, cord blood, cord tissue
  Seychelles Islands    Davidson et al 2005
   — at 5.5 years: no deficits in language, visual-motor integration, various
    cognitive domains

r Proj ect Viva (n= 13 5)  Oken et al 2006

maternal hair mercury
   - at 6 months : deficit in visual recognition memory
   — able to separate beneficial effects of fish consumption from harmful effects
                                                                RCT of dental amalgams in school-aged: no effect
    Mercury and Autism: Vaccines

  Controversy: thimerasol as preservative
  breaks down to ethyl Hg and thiosalicylate
  Polarization "Autism: a novel form of mercury
  poisoning" (Bernard et al)
  Removed from most childhood vaccines in 2001/02
  Numerous ecologic studies using before/after
  Few studies with individual-level data:
  Verstraeten et al of CDC... Vaccine Safety Datalink
  Rh" and thimerasol-containing rhogam
  Clarify: issue of MMR is unrelated
               Sources of Hg:
  Combustion of fossil fuels
  Consumption of seafood or ocean or freshwater fish
  Erosion of dental amalgams
  Occupational exposure from mining
  Direct contact from damaged mercury thermometers,
  blood pressure cuffs, barometers, incandescent lights,
  or batteries.
  Dermal absorption from skin-lightening cremes
  Use of nasal sprays, ear wax removal products, contact
  lens solutions
   Studies of (
) Hg & Autism
   Palmer et al (2006): TRS emissions inventory, Hg only & autism
   rates by school district
   Windham et al (2006): HAP model for multiple ambient
   Both were ecological

   Think about timing!!

                                                       *    ildhood  utism  isk from
                                                         enetics andJhe  nvironment
To identify causes and contributing factors
for childhood autism:
To determine mechanisms of susceptibility
for childhood autism

                                                      Mechanisms for Xenobiotics
                 Consumer products
                 Medical history

Autism or Developmental Delay
Population-based Controls
t H/\ Rr, r >
   Confirmation of diagnosis:
       Parents interviewed:


                                        Hair Hg measurement - time course
                                             JCG Hair, Root(O) to Tip (43),
Statistical Analysis
                                       1 .E-06
                                          13579 1113151719212325272931333537394143
                                        Log Hg and Covariates by Case Status

     Prediction of log(Blood Hg)'
Autism or ASD
Ate tuna (1+ servings/wk)
Ate ocean fish ( " )
Ate freshwater fish (" )
Beta    P-value
-0.01     0.95
0.56     0.001
0.68    O.0001
Hg amalgams x chew/grind teeth    0.15      0.004
Nasal spray or ear wax removal     0.5°      n no
* Multivariate analysis to adjust for confounding
 Subjects weighted to adjust for differential pa

                                                                      Timing: Current concentrations of blood metals in
                                                                      children 2-5 years of age unlikely to represent
                                                                      causal factors:
                                                                      possibly concommitant, or downstream of ASD,
                                                                      Some authors suggested abnormal metabolism or
                                                                      faulty excretion of metals in children with autism
                                                                      Statistical analyses validate use of questionnaire
                                                                      data about recent exposures to predict current
                                                                      blood Hg level
        Future Work on Metals
    Earlier time windows for causal factors:
     - Analyses of baby locks (first haircuts) currently
     — Newborn blood spots
     - Maternal hair (if long enough)
    Evaluate subsets: early onset/regressive
    Gene x environment interaction: GSTM1, GSTT1
    Develop a pharmacokinetic model of life-course
    Hg profiles (need funding!)
    Analysis of other metals: Pb, Cd, As, Mn

   Be in CHARGE !
         Grateful thanks to:
            Lesley Deprey
            Carrie Jones
         Beth Goodlin-Jones
           Susan Bacalman
       Nicole Tartaglia, Steve
      Nowicki, Jean Sakamura
            Melissa Rose
      Carola Gutierrez de King.
     Susana Gonzales, Caroline
      Grantz, Angelica Guzon.
         Eva Long, Cynthia
       Contreras, Devon Baird
Special Thanks to our Funders
                                                                             CHARGE  AU Pool  CHARGE  DD Pool  CHARGE
                                                                            AU (n=341)  (n=
                                                             Male sex of child
                                                             Parents' Race:
                                                                                        DD (n=54)  (n=299)  GP (n=lC
                                                                                                           GP Pool
                                                             One or Both Parents Hispanic
                                                             Mother's age >35 Years
                                                                 (at Birth of Child)
                                                             MotherOsEduation <12yrs
                                                                 Outside USA orMexicc

 "Genetic and Social Modifiers in
 Environmental Neuroepidemiology: The
 Role of Context in Chemical Exposure"

          Robert Wright MDMPH
         Department of Pediatrics,
        Children's Hospital, Boston,
    Department of Environmental Health
                                                                            • Fitted values
                                                     Biological Vulnerability

                                                     • Construction of the central nervous system
                                                       (CMS) begins in utero,
                                                     • Continues throughout childhood and
                                                       involves the production of 100 billion nerve
                                                       cells and 1 trillion glial  cells.
                                                     • Cell migrate, differentiate, and form
Transmits signals between neurons
 nEnvironmental stimuli will cause neurons to fire
 nNeuronal/synaptic firing is a signaling process to
  mold the synaptic architecture of the brain
How does the Brain Build this


• Some of it is stochastic
  nSynapses are made by the billions, and in
    some respects randomly, between neurons.
    We make a net gain in synapses from fetal life
    till about age 2 years
  nThen the number of synapses in our brain
    starts to decrease

Synaptic Networks
  Environmental Stimuli cause nerves to fire:
  When they fire neurotransmitters are released
  into synaptic junctions
    This releases growth factors- signals that this is an
    important neuronal connection (i.e. it gets used)
  In other words there is a "natural  selection"
   n Functional synapses release growth factors
   n Nonfunctional synapses do not release the growth
                                                                            Hebb Synapses
So how do Environmental

Chemicals affect Development?

• At "low" doses (blood lead around 5-10 ug/dL)
   n Lead will interact with Protein Kinase C
     • Stimulate neurotransmitter release
     • Neurons fire in the absence of an appropriate environmental
   n Lead mimics calcium
     • Calcium is critical to nerve signal transmission
     • Calcium enters neurons during depolarization
     • Lead blocks calcium channels
Lead and the  Brain
  Net effect
   n Lead stimulates nerves to fire in a more stochastic
   n Lead also inhibits neurotransmission (both
     appropriate neurotransmission and inappropriate
  Changes the underlying synaptic architecture, making it
  less efficient
  The brain's capacity to diminish the effects of
  toxic insults through structural/functional
    This occurs through the same processes as synaptic
    In other words plasticity allows for new connections to
    be made which improve function following an insult
  Maladaptive vs adaptive plasticity
Neurodevelopment and Social
      1 Chronic Stress known to impair
       memory and learning capacity

Non-chemical Toxicants-
Psychological Stress

• Psychological stress - activates HPA axis
 Increases cortisol
• Hippocampus - highest density of
 glucocorticoid receptors
  • modulate neuro and synaptogenesis
  • acutely, stress enhances memory formation,
  • chronic stress appears to inhibit it
Social Environment and Pb

• Guilarte et al
• Lead poisoned animals during lactation
• Randomized to 2 groups
  nAnimals raised in social isolation
   Animals raised in groups with social
    • Tested on memory in Water maze
                                                   Acquisition Time
                       Probe Test
                                                A.                |B.
                                                140,           .    £ 45.
                                               -120-               £ JO

                                               liu   ill*
                                                  E-HiU l-Hai  E-CB  I-PB    i ' E-H20 ' I-HSO ' E-Pb ' l-Pb
                                                      CondMon       f      Condlllon
         Enriched neuron
                  impoverished rwuron
Can Reducing Stress be a

• Mexico City
• Coopersmith self-esteem administered to
  mothers when child 24 months of age
• Cross-sectional analysis
• Covariates
   Blood Pb, mom's IQ, mom's education, child's

Main Effect of Maternal

md!24 | Coef P> 1 t [95% CI]

Blood Pb | -.11 0.569 -.50 .276
autoes | .46 0.006 .12 .78
Adjusted for Maternal IQ, education, Infant Sex,



"*'V*V- '-v Blood Pb and MDI
»Jfc* \S
/;^f^^*7T ~ Self esteem
• •' * =' ' . Quartile 1,2,3
-5 0 5 10 15 20
I"'"'"""'™' 	 F«.dv.lu.s |
!l?*!4lU— Hlv-^1— ' Self esteem
...•;;•/.• ' ' ' • Quartile 4
5 ° ,««»„,., 10 "
|«resldmdlvscov Fitted values |

Maternal Depression scale at delivery vs 24 month M Dl
       |o V24MentMDIC.
Another Pilot Study:  Maternal Child
Lung Study
• Pregnancy cohort recruited from 1986-1992
• Study of in utero/environmental tobacco smoke
  exposure and respiratory outcomes
• Women enrolled before 20th EGA week
• Children followed after birth
• Measured ETV (violence) and WCST as pilot
Effect of Cotinine in Predicting Errors on WCST:
Stratified by Median Violence Exposure

% Errors
# Perseverative
# Perseverative
% Perseverative
Cotinine Beta (Low
2.9 (p=0.6)
0.8 (p=0.9)
Cotinine Beta (High
9.8 (p=0.07)
11.1 (p=0.007)
9.9 (p=0.02)

                                                  How Does Genetics play into this?

                                                  • Genetics regulates synapse formation
                                                    n Maintenance
                                                       • Growth factors
                                                       • Protection from oxidative xenobiotics
                                                       • Nutrition

(A) Astrocytes increase synapse number by secreting cholesterol bound to large
lipoprotein particles containing apolipoprotein E (apoE).
(B) These particles are internalized by neurons, leading to increased cholesterol within neuronal
membranes. It is possible that apoE also activates yet to-be-identified signaling pathways within the neurons.
(C) These changes stimulate an increase in the number and efficacy of synapses.
From: Barres: Science, Volume 294(5545).November 9, 2001.1296-1297
                                                               APOE and Neurodegeneration

                                                               • E4 allele associated with 2-5 fold
                                                                 increased risk of AD if heterozygote
                                                                  D5-17 fold increased risk if homozygote
  APOE and Neurodevelopment

  • Study of lead exposure and infant
     development in Mexico.
  • Infants enrolled at birth, cord lead levels
     measured, Mothers receive calcium
     supplements in RCT.
  • Bayley Infant Development scales
     performed at 24 months of age.
APOE and Neurodevelopment

Multivariate Analysis   Beta
#APOE4              4.3(95% Cl: 0.03 - 8.5)

Study Group- subjects E4/E3. E4/E4
Referent group- subjects E3/E3, E3/E2, E2/E2
* OR adjusted for the maternal IQ, Sex, gestational
  age, dietary calcium, umbilical cord blood lead
  level and Maternal years of Education.
    Figure 1: Smoothed Plots of MDI Score vs Umbilical Cord
                     Lead Levels
       APOE2 or APOE3 Carrier
                                APOE4 Carrier
         Umbilical Cord Lead Level ug/dL
                                                                VT*V-fc '.
                                                                 A.*:. •;••.  ..,
                           C2 Genotype as Modifier
                           of Cord Pb Effect

                             Transferrin C2 Wildtype
                                                                                            Transferrin C2 Carrier

 Metal Mixtures

 • Just as exposure does not occur uniformly
  against a given social context.
 • Exposure to Neurotoxicants is mixed.
 • Both have evidence of neurotoxicity.
Mexico City
  Blood Mn measured on 300 infants at 1
  year of age from archived samples.
  Blood Pb measured at 12, 18 and 24
  Bayley MDI at 12, 18 and 24 months.
Blood Pb and 24-month MDI Association
Varies by Blood Mn Level
 Lowest 4 Quintiles of Blood Mn    Highest Quintile of Blood Mn
       Blood Pb (ug/dl)               Blood Pb (ug/dl)

        Interaction beta: -1.5, p=0.04 (N=290)
Manganese-Lead Interaction
Highest Quintile of Blood Mn x Blood Pb
Adjusted beta* p
12-month MDI
18-month MDI
24-month MDI
Repeated Measures
•Adjusted for 12-month blood Pb level, inf
-0.66 0.
-1.4 0.
-1.5 0.
-0.9 0.
ant sex, maternal IQ, maternal education
 Mexico Birth  cohort

 • The work just reviewed led to the
  establishment of a new birth cohort in
  Mexico City.
 • 1) R01 ES014930 Metal Mixtures and
 • 2) R01 ES013744 Stress, Lead, Iron
  Deficiency and Neurodevelopment.
Mexico City Birth Cohort

• Designed to study
  n Prenatal vs post-natal contributions to
   Genetic susceptibility
  n Metal mixtures
   Social modifiers of toxicity

Mexico City Cohort

• Long term goals
  D Identify factors that increase/decrease metal
    Understand the biology of metal neurotoxicity
  n Prevent toxicity
  nTreat toxicity after it has occurred
     Tar Creek Superfund Site
       The MATCH Study
     (Metals Assessment Targeting Community
                                                                     "Ga-Du-Gi"- Working Together
                           A^re in Mexico to
                             ... •

Adrienne Ettinger
Hector Lamadrid
David Bellinger
Rosalind Wright
Howard Hu
Lourdes Schnaas
Adriana Mercado

Tar Creek
Mary Happy
Rebecca Jim
Earl Hatley

         Criminal Behavior as a Late
        Outcome of Early Exposure to
              Environmental  Lead
               Kim N. Dietrich, Ph.D.
                          Environmental Factors in Criminal

                         Parental dysfunction
                         Community violence
                         Illicit Drugs
 f I, I'll- M
 Chi Id mf-.
    Biological Factors in Criminal

    Functional Anatomical Characteristics of
    Neurotransmitter Metabolism
    Autonomic Function
    Traumatic Brain Injury (Frontal Lobes)
    Genetic endowment (Functional
                      Criminal Behavior as an Outcome of
                            Childhood Lead Poisoning
                                                                                                        t Children's
          Lead Exposure and Juvenile
      Delinquency: Earlier Observations

  1943: Byers and Lord reported a high prevalence of behavior
      problems among survivors of lead encephalopathy.
      "...violent aggressive behavioral difficulties such as
      attacking teachers with knives and scissors."
     Byers & Lord, Am J Dis Child. 1943
                    Bone Lead Levels and Percentage of Children Scoring in the
                    Clinical Range for Aggression, Delinquency, and Attention on
                    the Achenbach Child Behavior Check List
                                             Needleman.etal., JAMA, 1996.
                                      Dr. Randolph Byers

V Children's
K Cincinnati
k Children's

  Bone Lead  Levels (ppm) in Adjudicated

    Delinquents: A Case Control Study*

              Cases            Controls        P value
              n    Mean(SD)    n   Mean (SD)

  All Subjects    195   11.0(32.7)   150   1.5(32.1)   0.007

  African-American 158   9.0(33.6)     51   -1.4(31.9)   0.05

  White        36   20.0(27.5)     95    3.5(32.6)   0.008

   'Needleman, et al. 2002, Neurotoxicol Teratol.
                                                                      Other Observations: Ecological Studies
                                                                       Stretesky and Lynch (2001) reported positive correlations between
                                                                       homicide rates and air lead contamination levels for 3111 counties
                                                                       in the US. Even after adjustment for 15 confounding variables, a
                                                                       four-fold increase in homicides in the counties with the highest air
                                                                       lead concentrations compared to counties with the lowest air lead
                                                                       concentrations was found.
                                                                                          Stetesky & Lynch, Arch PediatrMolesc Med., 2001

                                                                       Nevin (2000) reported a statistically significant relationship between
                                                                       trends in sales of leaded gasoline and violent crime after adjustment
                                                                       for such variables as unemployment rates and percent of population
                                                                       in the age range where there is a higher risk for criminal behavior.

                                                                                          Nevin, Environ Res., 2000
                                                                                                                  Chid n riiil i
                                                                                                                  Chi Id mf-.
     Limitations of Earlier Studies

  •  These studies suggest that exposure to
     environmental lead during childhood is
     associated with the development of behavioral
     problems, delinquency and criminality.
  •  Questions remain, however, because the
     majority of these studies were cross-sectional,
     relied on indirect measures of lead exposure or
     did not follow the children into adulthood to
     examine the relationship of lead exposure with
     persistent criminality.

"Cincinnati                FHBlKr,sr«,:              f
                                                                     The Cincinnati Lead Study of Juvenile
                                                                       Delinquency and Adult Criminality
                                                                              Cincinnati Lead Study catchment are;
    The Cincinnati  Lead  Study
   A prospective, longitudinal study initiated in
   1979 that is examining the  early and late effects
   of childhood  lead exposure on growth and
   development with a particular emphasis on
   neurobehavioral outcomes.
   The Cincinnati Lead Study has collected data on
   exposure (blood lead concentrations),
   neurobehavior, child health, and
   sociodemographic variables on a quarterly to
   yearly basis since its inception.
Cincinnati                511?"™,.™              Mb. Children's
                                                                     Blood Lead Concentrations in the Cincinnati Lead Study
                                                                                           ch, et al. Pediatrics, 1993.

      Association of Blood Lead Levels and Self-Reported
         Delinquency in 16 Year-Old Adolescents in the
                      Cincinnati Lead Study
                  Prenatal PbB

                  Average Childhood PbB

                  78 Month PbB
              Low est         Low        Medium

                            Blood Lead Level
   Dietrich, et al. 2001, Neurotoxicol Teratol.
                                    Cincinnati  Lead  Study Cohort as Adults
                                                           (N =  250)

                                    Subject Characteristics
                                                                                                                                        No. (°/y/Mean(SD)

                                                                                                                                          225 (90 0%)


                                                                                                                                           29(11 6%)
   Cincinnati  Lead  Study Cohort  as Adults
                          (N =  250)
  Maternal Characteristics

  Age at delivery (years)
  Maternal IQ (points)
  High School graduate
  HOME Inventory at age 3 (points)

  History of arrest (yes)

  Marital Status
                                                No. (°/
    Blood Lead Concentrations and Arrests for
  Violent Offenses in the Cincinnati Lead Study
Mechanisms: How Does Lead Increase
          Antisocial Behavior?
                     6     9     12     15
                     Six-year Blood Lead Concentration (ug/dL)
    Direct route: Lead affects brain systems that regulate social-
    emotional functioning, Including neurotransmltter metabolism
    and function, and neural growth, survival and differentiation In
    critical areas such as prefrontal cortex Gene-environment
    interactions may also play a role.
    Indirect route: Early lead exposure Is associated with higher
    rates of school failure and reading disabilities. Students who do
    poorly In school are more likely to engage In delinquent and
    criminal activities.
C Cincinnati
S Children's
                                         /» Chid n riiil i
Thn Costs nf Sprawl

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ttontufi lnmiww«ri.!«. t*t i I?H-piy*
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              ipact development patterns prodi*

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      Vehicle IVf les Traveled

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                                                                                              Urban Sprawl

                                                                                              and Public Health


                                 s to Children Walking to or From School-United States, 2004
                                      n [»rt of *> octa* Htiltfn th»1



          Street Network
Typical Subdivision
   Cu I-de-Sacs

\\.iik-otul.i (II) Sdionl H.ins HiU".

Voters say no to 'mega-campus'
1^ '•<>,:: g
                             Challengers overwhelm
                             incumbents to w in seats on
                             Pottsiwn School Board
                             KIUVIIWN - Votan *

                                                                          Renovate or Replace?,
Travel end Environmental
ImpBcations of School Slug
                                                        Expert tests walking routes

  For more information..

- My Contact information:
- Tim Torma
- torma.tim@epa.gov
- 202-566-2864

- www.epa.gov/smartgrowth/schools

 Environews Spheres of Influence
Community Impacts of Goods Movement
                      VOLUME 1161 NUMBER 2 I February 2008 • Environmental Health Perspectives

                 Spheres of Influence  Global Trade Comes Home
      For many U.S. residents, 2007 was  a year of heightened
      awareness of some  of the problems of global  trade.
      Extensive recalls  of melamine-tainted pet food in the spring
followed by even larger toy  recalls in the summer and fall raised
consumer concerns about how the United States can ensure the
safety of products shipped in from overseas. The Salt Lake Tribune
and the Wall Street Journal detailed injuries  and illnesses threaten-
ing the health of Chinese  workers making products for export to
the United States. And on 15 December 2007, a New York Times
feature detailed the practice of farming fish in toxic Chinese waters
for export to the United States and other countries.
   While these news stories demonstrate some of the pitfalls of
globalization, much less attention has focused on air pollution and
other community-level  impacts in the United States, as toys,  elec-
tronics, food, and  other imports  travel through ports, then to
trucks, trains, warehouses, and stores in a complex system called
"goods movement."  Along the route, residents are exposed to diesel
exhaust and other vehicle emissions, noise  from truck-congested
roads, bright lights from round-the-clock operations, and other
potential health threats.
   Transportation experts refer to  these impacts simply as "external-
ities"  of transport, but to  community residents they can directly
harm the quality of daily life.  As ports and goods movement activity
expands throughout the United States, a major challenge is how to
make its health and community impacts a more central part of policy
Economic Benefits, Community Costs
Economic development advocates call the side-by-side ports of Los
Angeles and Long Beach Southern California's "economic engine."
Combined, they handle the most containers of any U.S. port.
With more than 40%  of all imports for the entire United States
coming  through the Los Angeles/Long Beach port complex,
according to the U.S. Department of Transportation, the ports are
critical to the national economy. A March 2007 national economic
impact study by the twin ports reported  that imports coming
Children play soccer next to the TraPac terminal at the Port of Los Angeles,
Wilmington, California.
                                                        A 79

Spheres of Influence   Global Trade Comes Home
through the complex generated jobs, income,
and tax revenue in every state of the nation.
    While recognizing the economic impor-
tance of international trade, the  U.S.
Environmental Protection Agency (EPA) has
called the movement of freight a "public
health concern at the national, regional and
community level." In a 22 August 2007
Federal Register announcement of a meeting
of its National Environmental Justice
Advisory Council (NEJAC),  the  EPA also
described mounting evidence that local com-
munities adjacent to  ports and heavily traf-
ficked goods movement corridors are the
most significantly  impacted by the  goods
movement system.
    The  ports of Los Angeles/Long  Beach
combined contribute more than 20% of
Southern California's  diesel particulate pollu-
tion and are the single largest source of pollu-
tion in Southern California,  according to  the
South Coast Air  Quality Management
District (AQMD), the region's air quality reg-
ulatory agency. The California Air Resources
Board (GARB), in its 2006  Emission Reduc-
tion Plan for Ports and Goods Movement, cal-
culated that in California  alone there  are
2,400 premature heart-related  deaths related
to port  and goods movement pollution,
62,000 cases of asthma symptoms,  and more
than 1  million respiratory-related school
absences every year. Nationwide, reports
James Corbett of the  University  of Delaware
and colleagues in the 15 December 2007 issue
of Environmental Science & Technology, an
estimated 60,000 lives are lost prematurely
every year due to ship emissions, which are
virtually unregulated.
    Recent research findings about living close
to traffic emissions add to concerns. A study
by investigators at the University of Southern
California (USC),  published 17  February
2007 in  The Lancet, showed that  children  liv-
ing near freeway traffic had substantial deficits
in lung function development between the
ages of 10 and 18 years, compared with chil-
dren living farther away. "Since lung develop-
ment is nearly complete by age eighteen," says
lead author W. James Gauderman, "an indi-
vidual with a deficit at this time will probably
continue to have less than healthy lung func-
tion for the remainder of his or her life."
    Other studies published in the February
2003 and September 2005 issues of EHP
linked traffic exposure to increased risk for
low birth weight and premature birth. A new
study published 6  December 2007  in the
New England Journal of Medicine showed that
adults with asthma who spent just 2 hours
walking  on  a street with heavy diesel traffic
suffered  acute transient effects on their lung
function along with an increase in biomarkers
that indicate lung and airway inflammation.
In addition, research by the EPA-funded
Southern California Particle Center  at the
University of California, Los Angeles, pub-
lished in the April 2003  issue  of EHP,
demonstrated that ultrafine particles from
incomplete combustion of engine  fuels and
lubricating oils can bypass the body's defense
mechanisms, gain  entry to cells and tissues,
and alter or disrupt normal cellular function.

Regulation to Date
In 2005, GARB issued guidelines that recom-
mend avoiding construction of new schools
and homes within a mile of a railyard or
500 feet of a busy highway. A few years  earlier,
California legislators,  citing health effects
research findings, passed  SB  352, a law pro-
hibiting building new schools within 500 feet
of a busy road or freeway. But the  2003 law
permits several loopholes, such as allowing a
school district to show that it is able to mitigate
traffic emissions so that pupils and staff will
suffer no significant health risk. The law also
requires that  a school district verify that any
railyard within a quarter mile of a new school
will not present a public  health threat. Some
school  districts,  in  the scramble to build new
facilities, are continuing  to site new schools
near freeways and rail operations.
   Conversely, railyards and freeways also
continue to be proposed in close proximity to
schools and homes, such  as a proposed truck
expressway to speed trucks away  from the
Southern California ports, which would pass
within 100 feet of homes and 700 feet of a
local school. The draft environmental impact
statement (EIS) for the project,  issued in
August 2007 by the California Department of
Transportation  (Caltrans) acknowledges the
scientific research:  "Some recent studies have
reported that proximity to roadways is  related
to adverse health outcomes—particularly res-
piratory problems." But  the EIS goes on to
say that using these studies  to determine if
there will be adverse impacts  from  the truck
expressway project is premature.
   According to Ron Kosinski, deputy dis-
trict director for the Caltrans district covering
Los Angeles  County, the Federal  Highway
Administration (FHWA)  is delaying any pol-
icy decisions related to health  effects from
proximity to  traffic until  the conclusion of a
review  of all the studies by the Health Effects
Institute—a report that  is not expected  for
several years.  FHWA  spokesman  Doug
Hecox says, "[The agency is] not suggesting
that nothing should be done. But there  are
no conclusive studies right  now drawing a
direct  relationship between the number of
trucks  on a road and the percent of impair-
ment of an affected child."
   Environmental, community, and  public
health groups have  long pressured Los Angeles
and Long Beach  port authorities to take
action  on port pollution.  In 2006, an historic
agreement called the Clean Air Action Plan
(CAAP) was signed, vowing that the ports
would reduce air pollution by 45% within the
next 5 years. However, some community and
environmental groups are concerned that the
deadlines set in the CAAP are slipping.
    Port of Los Angeles executive  director
Geraldine Knatz responds that the CAAP "is a
five-year process that requires major invest-
ment in construction and new equipment, and
in the interim, cargo  movement through our
ports continues." Knatz also points to a new
program to reduce port-related truck emis-
sions by 80% by 2012—a $2 billion  initiative
that she  says  "cannot simply  happen
overnight."  In  December 2007, both ports
adopted container fees to fund the replace-
ment of 17,000 polluting big-rig trucks with
new models that meet tighter EPA diesel emis-
sion standards.
    At the state level,  GARB issued new rules
in December 2007 that would require ships
to plug in to electricity rather than using
diesel auxiliary engines when docked in the
harbor and that would require stricter emis-
sions standards for trucks frequenting ports
and railyards. The South Coast AQMD has
long championed stricter controls on ports
and rail operations to  protect public health, as
well as environmental justice  considerations.
In 2006 the agency issued rules to reduce pol-
lution from idling locomotives in railyards,
but railroad companies sued to block them.
In 2007 a Los Angeles-based U.S. District
Court judge struck down the agency's rules,
arguing that it lacked  authority to adopt
them; the agency is appealing the decision.
    According to the South Coast AQMD,
emissions from ships  are also underregulated,
with no significant international or federal
emission control regulations. In 2004, the
EPA announced plans to put in place new
standards for ships  and locomotives. On
15  January 2008, the Greenwire news service
reported these standards were under review at
the White House Office of Management and
Budget, which must approve them before the
EPA can sign off on them.

Increased Trade Expected
The health and environmental justice impacts
of port, rail,  and trucking pollution are not
limited to  California. In South Carolina, for
example, environmental groups and home-
owners are troubled by anticipated impacts of
a proposed terminal expansion at the old
Charleston Navy Base, which the South
Carolina Coastal Conservation League says
will triple the container volume through
Charleston and generate thousands more
truck trips a day through a low-income black
neighborhood. "An access road and off-ramp
will go right through  our Rosemont  commu-
nity as trucks leave the port terminal for the
A 80
                     VOLUME 1161 NUMBER 2 I February 2008 •  Environmental Health Perspectives

                                                                               Spheres of Influence    Global Trade Comes Home
nearby interstate highway," New Rosemont
Neighborhood Association president Nancy
Button told participants of a recent commu-
nity-academic conference on port health
impacts held in Los Angeles.
    According  to  The Journal of Commerce
Online (JoC), a news magazine covering inter-
national  trade  and goods movement, many
U.S. ports are expanding in hopes of capitaliz-
ing on rising international trade volumes.
Historically, says maritime industry economist
Bill Ralph, as quoted in the 16 January 2008
JoC, international container trade in the
United States has an annual growth of about
7%. In 2006, U.S. containerized imports grew
by 11%. But  in 2007,  says Ralph, they
increased by only 3%, due to  a slowdown  in
the housing and auto markets. Economist
Walter Kemmsies, quoted 2 days earlier in the
JoC, predicts that U.S. container trade will
return to its normal 7% annual growth within
the next 2 years and continue to grow steadi-
ly—even faster if the United States enters into
more free trade agreements.
    The EPA Office of Environmental Justice
(OEJ) has taken note of the  growth trends
and the rising environmental health concerns
about port and goods movement expansion.
In August 2007, acting OEJ director Charles
Lee appointed a new working group to  study
the impacts of ports and goods  movement
through an "environmental justice lens,"
with a report expected in June 2008.  Land
use decision making will be 1  element in the
report, along with community participation,
regulatory mechanisms, innovative technolo-
gies, and more.
    Projected increases in foreign trade,  along
with many states' planned expansion of high-
ways, rail facilities, and ports to handle Asian
imports, cause concern about increased air
pollution if regulations to reduce emissions
do not keep pace with trade growth. In the
22 August  2007 Federal Register, the EPA
noted that the anticipated increase in  trade
will have air quality impacts,  and the agency
threw out a challenge to the ports and com-
panies involved in goods movement:  "It is
becoming increasingly important that these
entities operate sustainably, i.e., economically
viable, environmentally and socially  responsi-
ble, safe and secure."

Community Response
As this global goods movement system
expands,  communities across  North America
are now recognizing that they are facing simi-
lar circumstances and common conflicts. And
they are banding together, in small and large
coalitions, to address the impacts.
    In the 1990s, just a few groups such as the
Sierra Club, the Environmental Health Coali-
tion, the Center for Community Action and
Environmental Justice, and homeowners near
the ports were focused on the effects of the global
supply chain.  But 2001 turned out to be a
watershed year.  That year, the Natural Resources
Defense Council, the Coalition for Clean Air,
Communities  for a Better  Environment, and
2 harbor-based homeowner's associations filed a
lawsuit challenging the Port of Los Angeles's
environmental  review of planned construction
for a major shipping terminal. Two years later
they won a $50 million landmark settlement
from the city requiring environmental mitiga-
tions, such as the "plug in" rule issued by GARB
in December. A new era had begun—one that
started to shift public attention from the role of
international trade simply as the region's major
economic engine to the potential  perils of
uncontrolled goods movement expansion.
   That same year, the  NIEHS-funded
Southern California Environmental Health
Sciences Center, based at USC, held a town
meeting to share its research findings with
community groups, residents, workers, and
policy makers. In turn, scientists heard the
emerging concerns of residents about diesel
emissions near the ports, railyards, and ware-
houses. Research findings on the health
impacts of air pollution soon began to find
their way into  policy debates on goods move-
ment and port expansion.
   Over the next 5 years,  multiple partner-
ships started to come together to specifically
address issues  of ports and goods movement
in California. Among the collaborative efforts
active today are the Ditching Dirty  Diesel
Collaborative based in Oakland,  aimed at
developing a regional strategy to reduce diesel
emissions; the  Trade, Health & Environment
(THE) Impact  Project, a community-
academic collaborative aimed at  elevating
community voices  in the goods movement
policy debate and using science-based infor-
mation to  inform public policy; the Port
Work Group  of Green LA, which aims to
ensure that the Port of Los Angeles becomes
truly green, with the support of the city's
mayor; and a broad-based coalition  aimed at
improving wages and working conditions
(including  less-polluting  vehicles)  for port
truck drivers.
   Elsewhere, residents in  a neighborhood
near the Port  of Seattle have been counting
big-rig trucks parked overnight in their com-
munity in an effort to keep port-related pollu-
tion, safety hazards, and blight out of their
neighborhoods. In Arizona, a school superin-
tendent has asked officials not to enact zoning
changes that would allow construction of a
major intermodal facility (a railyard  at which
cargo is transferred between trucks and trains)
across the  street from a  local elementary
school. And on Long Island,  residents are ask-
ing the state of New York to reconsider its
plans to build an intermodal facility near resi-
dential communities and a wildlife preserve.
Tools for Action
Many groups  impacted by ports and goods
movement came together in late 2007  at
Moving Forward, the first North American
community-oriented gathering on this topic,
which was organized by THE Impact Project
and cosponsored by private groups along with
NIEHS- and EPA-ftinded centers.
   Participants  shared information on cur-
rent  health research related to goods move-
ment,  community concerns about health
impacts,  future goods movement expansion
projects (such as plans to deepen the harbor at
the Port of Savannah, Georgia, to handle larg-
er ships carrying twice as many containers),
and  community efforts to  effect change.
Presenters described tools for action, such  as
methods for mapping goods movement activ-
ities  in communities; understanding who the
key goods movement stakeholders and deci-
sion  makers are; ways to incorporate credible,
current scientific research findings into educa-
tional and policy efforts; and new methods
for developing health impact assessments.
   Eric Kirkendall from Kansas was struck
by the commonalities at the conference. Back
home,  he had formed the Johnson County
Intermodal Coalition in response to proposals
to build an intermodal railyard near the small
town of Gardner and surround his 4-acre
homestead on 3 sides with 12-acre warehouses.
Kirkendall says, "We sometimes feel alone  in
Kansas. But by the end of the conference I
understood that we are  not alone. We have
much to share with, and learn from, other
groups with similar challenges, as well as from
scientists and policy makers."
   Some  attendees thought more attention
should be focused on American consumer
habits,  a point echoed by Rev. Peter Laarman,
executive director of Progressive Christians
Uniting. He urges a closer look at the hidden
costs of imports. "Americans  think of them-
selves as consumers rather than as citizens," he
says.  "We don't care, for example, if Chinese
workers toil in factories with no safety regula-
tions, or if residents in communities near our
ports have to breathe dirtier air. What we care
about is 'How much do I have to pay for an
iPod?'  and 'Where can I buy this doll for
under ten dollars?'"
   By their very nature, the ports and goods
movement debates faced by community
groups throughout North America can help  to
inform future  discussions about consumerism
and globalization. As far as health effects go,
however, research findings and community
experience are strongly suggesting that global
trade, while an apparent boon to our economy,
will continue to  pose a serious threat to our
population's environmental health unless pro-
tective and collective action is taken, and soon.

                           Andrea Hricko
Environmental Health Perspectives  • VOLUME 116 I NUMBER 2 I February 2008

Research Partnerships Program Director
National Children's Study
National Institute of Child Health and Human Development/NIH/DHHS
2007 Children's Environmental Health
  W IV»  U |J • C I rt
October 12, 2007
US Department of Health
and Human Seivices

                                    US Environmental
                                    Protection A9ency

Authorized in 'The Children's Health Act of 2000':
study effects of the environment on child health and
Environment broadly defined:
chemical, biological, physical, psychosocial-cultural
Gene-environment interaction and gene expression
Largest/longest such study ever conducted in the U.S.
Lpngitudinal study of 100,000 children, from before
birth (even before conception) through age 21
Representative sample of children across the U.S.
Power to study important but uncommon outcomes   0
National resource for future research

Identify environmental effects on children:
   - harmful, harmless, and helpful
   - in the context of gene-environment interaction

Identify preventable causes of important
 health-related conditions in children

Provide  evidence-based data to guide decisions
 regarding children's healthcare and health  policy s°

Program Office (PO) at NICHD - NCS Director,
scientists, administrative staff
Interagency Coordinating Committee - NICHD, CDC,
Chartered Advisory Committee
Federal Consortium: key government agency reps
Steering Committee - Study Center Pis,  federal
scientists and community representatives
Coordinating Center - Data management/coordination
Study Centers - 7 Vanguard Centers & 22 new Cente^
Study Assembly - 4500  interested scientists & othei

National Children's Study Locations

Map Legend

%  2007 Locations

   Vanguard Locations

®  2008-2010 Location*





cultural Milieu
Housing quality,

phthalates, heavy

Infectious agents,
endotoxins, diet

Interaction between
factors and genes

Families, SES,
institutions, social
Priority Health
    & Behavior
                                            Obesity & Physical
Preterm, Birth


Head trauma,
incidence and
altered puber

Leveraging the
National Children's Study
The Research Plan or Protocol...
The potential links between
 exposure & outcome measures.,
The ongoing research findings
 as the Study progresses...

will spark  ideas for
 further research
 leveraging the core study
 ->adjunct study proposals

• Involve a subset of the NCS cohort

• Modular, focused studies utilizing NCS
 infrastructure: participants, and/or
 bio-specimens, and/or environmental

 Initiated by: government scientists,
 Study Center scientists, independent
 investigators, research advocates,

 •a unique research interest/capability
 •a specific public health or community
Utilize, complement, leverage the core
protocol for mutual benefit
"Outside' (not core-NCS) funding     oNjr"

• Scientific merit
• Public health importance: potential
 contribution to health care or policy
•AFit' with the NCS (priority exposure
 or outcome, sampling, tools, timing...)
•Appropriate use of bio-specimens and
 environmental samples

Burden on participants (time,
Burden on the Study infrastructure
Human Subjects issues: ethical &
legal considerations
Peer review, IRB review, funding

Brief electronic Preliminary Application

The Full Application is provided after NCS
approval of the Preliminary Application

Iterative process to facilitate timely
review of proposals: Program Office, ICC,
Steering Committee, Sample Oversight

"Partnerships' with government agencies
(e.g. intramural scientists and funding;
RFAs to extramural scientists...)

Government grants (e.g. R-01...)

Public-private partnerships: industry,
foundations, academia, research advocacy
groups, etc.

July 2008 to July 2009: VC pilot year

July 2009: Enrollment begins at
Vanguard and new Study Centers for
the Afull Study'

Adjunct Study proposals for pre-
conception, pregnancy, delivery,
newborn  and early infancy periods
could be submitted soon to commence

• Opportunities will continuously arise for
 additional research by leveraging the NCS

 Opportunities exist for public-public
 (other government agencies) and public-
 private partnerships

• Adjunct studies will broaden and enhance
 the NCS contribution to children's
 environmental health

• On the NCS website:

  • "Adjunct Study Overview'

  •Application for adjunct study proposal

  Marion J. Balsam M.D.

Research Partnerships Program Director

    The National Children's Study
     /w.N     ilChild       ly-gc
           cs@r   il.nih.

          Adjunct Studies:

      Tools for Recovery and
    Communicating Risks After
         Hurricane Katrina
 Objectives of Today's Panel

Describe the collaborative PEHSU
response to Hurricanes Katrina and Rita
(Debra Cherry, MD)
Experience and feedback from a Gulf
Coast pediatrician at Ground Zero (Scott
Needle, MD)
New tool: The NIEHS Hurricane Response
Portal (Marie Lynn Miranda, PhD)
Disaster Strikes: Aug 29, 2005

Over 354,000 Gulf Coast homes
Over 200 sewage treatment plants and
140 oil and gas platforms damaged
Rampant mold growth
Mountains of debris
Widespread demolition/reconstruction
Residents in temporary housing
  Tyler: The closest PEHSU
                               Tyler, TX to
                              New Orleans:

                               424 miles
      In Katrina's Wake...

"This is the mother of all multidisciplinary
problems"-John McLachlan, Tulane/Xavier
Research Scientist*
"The public health community must articulate
key health issues, keep the message simple and
focused, and develop effective strategies to
provide targeted timely results" - Kellogg
Schwab, Johns Hopkins Bloomberg School of
Public Health*
*Lessons Learned, In Katrina's Wake, EHP 114
(1): Jan 2006, pg A39

         Joint Documents and


   NYC, Atlanta, and Tyler PEHSUs
   - Clinician recommendations for return of children to
     previously flooded and/or hurricane impacted areas
   EPA: Siobhan McNally (Boston PSR), Martha
   Berger, Michael Shannon
   - Tip Sheets for Parents - Mold, sludge
   - Environmental Questionnaire for Clinicians
   More Recently - Poor indoor air quality in FEMA
   - Formaldehyde fact sheet
     Sample Call: Formaldehyde,

                July 2007
A mother called
SWCPEH regarding
her 6 y/o daughter
with a nasal polyp
and nosebleeds
several times per
month. She and her
daughter have been
living in a FEMA
trailer in the New Orleans area since Katrina (almost 2
years as of July). The girl has no known allergies, and
the problems started in the last year. Mom wants to
know if this could be  related to formaldehyde.
"My home"; www.fematrailersong.com
                                      Sample Call: Sludge, Sep 2005
                                  A mother of three children,
                                   ages 8, 4, and 3 months,
                                   called about moving back
                                   to her home that had
                                   standing water for 3
                                   weeks and sludge
                                   contaminants from an oil
                                   refinery spill. The refinery
                                   offered to remove the soil
                                   from her yard and sludge
                                   from her home.
Photo: Clip art from PowerPoint
                                      Summary: SWCPEH/PEHSU
                                      Network Hurricane Response

                                    Prepared guidelines for returning children
                                    to previously flooded areas
                                    Prepared fact sheets and questionnaires
                                    in conjunction with EPA, PSR
                                    Answered calls from concerned parents

                                                                 Children's Environmental Health Initiative
                                                                        A research, education, and outreach
                                                                             program committed to fostering
                                                                         environments where all children can
                                12 October 2007
New Orleans: Before and After Hurricane Katrina
                                                                   Regional Overview
  Extent of Flooding
Industrial Canal Levee Breach
                                                          Lower 9th Ward Pre Katrina
                                                                                     Lower 9th Ward September 1st, 2005

                                                                      Lower 9th Ward December 14th, 2005
                                                     , —-=•-=•«•

         Key Health Consequence Questions
          NIEHS Response: Web Portal
• Mold and respiratory health
• Contaminant transport
• Solid waste management
• Mental health
•Build and maintain extensive data archive designed
 to investigate environmental health consequences of
 the hurricanes
•Provide a collaborative workspace for analysis of
 georeferenced data
•Provide a Gulf Coast resource to support
 environmental health research more broadly
         Collaborative Team
•Columbia University (ClESIN)
•University of Kentucky
•Research Triangle Institute
•San Diego State University
• University of California, San Diego
•Duke University
         NIEHS Hurricane Response Web Portal
                                                                                        i. 0

 Analysis Tools
Models for Customizing Research Environments
                    field of
Project Based Research Environment
  Custom Reports
Defining the Geographic Scope


Children's Protection in the Aftermath of „
 Natural Disaster: Tools for Recovery and
         Communicating Risks
      Tales from Ground Zero:

   Hurricane Katrina and Pediatric
   Environmental Health in Coastal
        Scott Needle, MD, FAAP
           October 12, 2007

Risks after Katrina:
and in-betweens
I Mold
  Gastrointestinal illness
 > "Katrina Cough"
 • "Katrina Brain"
 1 Psychological trauma and the honeymoon
Lessons Learned
   lurring the line b/t "public" and "private"
  Shortage of resources in disaster area
  Communication is the priority
  Keep eyes and ears open
  Flexibility and ingenuity